Review
. 2013 Feb; 13:5.

CTLA-4 blockade in tumor models: an overview of preclinical and translational research

Joseph F Grosso 1 Maria N Jure-Kunkel  
Affiliations
  • PMID: 23390376
  •     102 References
  •     156 citations

Abstract

Cytotoxic T lymphocyte antigen-4 (CTLA-4) is a key negative regulator of T cell activation. A complex integration of positive and negative co-stimulatory signals in the well-defined B7:CD28/CTLA-4 pathway modulates the generation and maintenance of immune responses. Inhibiting negative regulation through binding of CTLA-4 has been shown to promote stimulation of adaptive immunity and potentiation of T cell activation. CTLA-4-blocking antibodies have demonstrated efficacy in various murine malignancy models when administered as monotherapy; additionally, they have shown synergistic anti-tumor activity when utilized with other agents, such as vaccines, chemotherapy, and radiation. Preclinical studies have supported the rationale for current clinical development of anti-CTLA-4 antibodies, including ipilimumab and tremelimumab, as novel therapeutic strategies to augment anti-tumor immunity in cancer. Both ipilimumab and tremelimumab have been evaluated extensively in melanoma; notably, ipilimumab was recently approved as monotherapy for the treatment of advanced melanoma. Tremelimumab is currently undergoing evaluation in phase II trials as monotherapy in melanoma and malignant mesothelioma, while ipilimumab is under clinical investigation in phase II and III trials in various tumor types, including in melanoma, prostate, and lung cancers as monotherapy and with other therapeutic modalities, such as chemotherapy and radiation. In this review, we will provide a detailed overview of preclinical advances that have delineated many features of CTLA-4 and have helped define its role in T cell response. We will also highlight clinical application of anti-CTLA-4 therapy in cancer and describe knowledge gaps that future studies may address.

Keywords: CTLA-4; T cell; antibody; co-stimulation; preclinical.

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Free PMC article 
Transduction of the cytoplasmic domain of CTLA-4 inhibits TcR-specific activation signals and prevents collagen-induced arthritis.
Je-Min Choi, Seung-Hyung Kim, +7 authors, Sang-Kyou Lee.
Proc Natl Acad Sci U S A, 2008 Dec 11; 105(50). PMID: 19066215    Free PMC article.
Fractionated but not single-dose radiotherapy induces an immune-mediated abscopal effect when combined with anti-CTLA-4 antibody.
M Zahidunnabi Dewan, Ashley E Galloway, +4 authors, Sandra Demaria.
Clin Cancer Res, 2009 Aug 27; 15(17). PMID: 19706802    Free PMC article.
Highly Cited.
Ipilimumab plus dacarbazine for previously untreated metastatic melanoma.
Caroline Robert, Luc Thomas, +21 authors, Jedd D Wolchok.
N Engl J Med, 2011 Jun 07; 364(26). PMID: 21639810
Highly Cited.
CTLA-4 is a second receptor for the B cell activation antigen B7.
P S Linsley, W Brady, +3 authors, J A Ledbetter.
J Exp Med, 1991 Sep 01; 174(3). PMID: 1714933    Free PMC article.
Highly Cited.
CTLA-4 blockade enhances the therapeutic effect of an attenuated poxvirus vaccine targeting p53 in an established murine tumor model.
Jonathan Espenschied, Jeffrey Lamont, +4 authors, Joshua D I Ellenhorn.
J Immunol, 2003 Mar 11; 170(6). PMID: 12626601
Manipulation of T cell costimulatory and inhibitory signals for immunotherapy of prostate cancer.
E D Kwon, A A Hurwitz, +5 authors, J P Allison.
Proc Natl Acad Sci U S A, 1997 Jul 22; 94(15). PMID: 9223321    Free PMC article.
Highly Cited.
Cancer immunoediting: integrating immunity's roles in cancer suppression and promotion.
Robert D Schreiber, Lloyd J Old, Mark J Smyth.
Science, 2011 Mar 26; 331(6024). PMID: 21436444
Highly Cited. Review.
Cytotoxic T-lymphocyte-associated antigen-4.
April K S Salama, F Stephen Hodi.
Clin Cancer Res, 2011 Apr 07; 17(14). PMID: 21467163
Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection.
Shawn D Blackburn, Haina Shin, +7 authors, E John Wherry.
Nat Immunol, 2008 Dec 02; 10(1). PMID: 19043418    Free PMC article.
Highly Cited.
The emerging role of CTLA4 as a cell-extrinsic regulator of T cell responses.
Lucy S K Walker, David M Sansom.
Nat Rev Immunol, 2011 Nov 26; 11(12). PMID: 22116087
Highly Cited.
The anti-tumor activity of anti-CTLA-4 is mediated through its induction of IFN gamma.
T J Paradis, E Floyd, +5 authors, R P Gladue.
Cancer Immunol Immunother, 2001 Jun 23; 50(3). PMID: 11419179
Combination immunotherapy of primary prostate cancer in a transgenic mouse model using CTLA-4 blockade.
A A Hurwitz, B A Foster, +5 authors, J P Allison.
Cancer Res, 2000 May 16; 60(9). PMID: 10811122
Highly Cited.
Treatment of transplanted CT26 tumour with dendritic cell vaccine in combination with blockade of vascular endothelial growth factor receptor 2 and CTLA-4.
A E Pedersen, S Buus, M H Claesson.
Cancer Lett, 2005 Jun 02; 235(2). PMID: 15927356
Human CTLA4 knock-in mice unravel the quantitative link between tumor immunity and autoimmunity induced by anti-CTLA-4 antibodies.
Kenneth D Lute, Kenneth F May, +8 authors, Yang Liu.
Blood, 2005 Jul 23; 106(9). PMID: 16037385    Free PMC article.
Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4.
E A Tivol, F Borriello, +3 authors, A H Sharpe.
Immunity, 1995 Nov 01; 3(5). PMID: 7584144
Highly Cited.
Hallmarks of cancer: the next generation.
Douglas Hanahan, Robert A Weinberg.
Cell, 2011 Mar 08; 144(5). PMID: 21376230
Highly Cited. Review.
Combination of CTL-associated antigen-4 blockade and depletion of CD25 regulatory T cells enhance tumour immunity of dendritic cell-based vaccine in a mouse model of colon cancer.
Asim Saha, S K Chatterjee.
Scand J Immunol, 2010 Apr 14; 71(2). PMID: 20384858
B7-1 or B7-2 is required to produce the lymphoproliferative phenotype in mice lacking cytotoxic T lymphocyte-associated antigen 4 (CTLA-4).
D A Mandelbrot, A J McAdam, A H Sharpe.
J Exp Med, 1999 Jan 20; 189(2). PMID: 9892625    Free PMC article.
CTLA-4-Ig regulates tryptophan catabolism in vivo.
Ursula Grohmann, Ciriana Orabona, +8 authors, Paolo Puccetti.
Nat Immunol, 2002 Oct 09; 3(11). PMID: 12368911
Highly Cited.
Improved survival with ipilimumab in patients with metastatic melanoma.
F Stephen Hodi, Steven J O'Day, +26 authors, Walter J Urba.
N Engl J Med, 2010 Jun 08; 363(8). PMID: 20525992    Free PMC article.
Highly Cited.
Combination immunotherapy of B16 melanoma using anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and granulocyte/macrophage colony-stimulating factor (GM-CSF)-producing vaccines induces rejection of subcutaneous and metastatic tumors accompanied by autoimmune depigmentation.
A van Elsas, A A Hurwitz, J P Allison.
J Exp Med, 1999 Aug 03; 190(3). PMID: 10430624    Free PMC article.
Highly Cited.
Antitumor activity in melanoma and anti-self responses in a phase I trial with the anti-cytotoxic T lymphocyte-associated antigen 4 monoclonal antibody CP-675,206.
Antoni Ribas, Luis H Camacho, +10 authors, Jesus Gomez-Navarro.
J Clin Oncol, 2005 Oct 06; 23(35). PMID: 16204013
Highly Cited.
Blockade of CTLA-4 decreases the generation of multifunctional memory CD4+ T cells in vivo.
Marion Rudolph, Katrin Hebel, +2 authors, Monika C Brunner-Weinzierl.
J Immunol, 2011 Apr 12; 186(10). PMID: 21478403
Foxp3+ CD25+ CD4+ natural regulatory T cells in dominant self-tolerance and autoimmune disease.
Shimon Sakaguchi, Masahiro Ono, +6 authors, Takashi Nomura.
Immunol Rev, 2006 Aug 15; 212. PMID: 16903903
Highly Cited. Review.
IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity.
V Shankaran, H Ikeda, +4 authors, R D Schreiber.
Nature, 2001 Apr 27; 410(6832). PMID: 11323675
Highly Cited.
Invariant natural killer T cells regulate breast cancer response to radiation and CTLA-4 blockade.
Karsten A Pilones, Noriko Kawashima, +3 authors, Sandra Demaria.
Clin Cancer Res, 2009 Jan 17; 15(2). PMID: 19147765    Free PMC article.
Lymphoproliferation in CTLA-4-deficient mice is mediated by costimulation-dependent activation of CD4+ T cells.
C A Chambers, T J Sullivan, J P Allison.
Immunity, 1998 Jan 16; 7(6). PMID: 9430233
Highly Cited.
Polychromatic flow cytometry: a rapid method for the reduction and analysis of complex multiparameter data.
Ulf Petrausch, Daniel Haley, +3 authors, Edwin Walker.
Cytometry A, 2006 Nov 08; 69(12). PMID: 17089357
Immune-mediated inhibition of metastases after treatment with local radiation and CTLA-4 blockade in a mouse model of breast cancer.
Sandra Demaria, Noriko Kawashima, +4 authors, Silvia C Formenti.
Clin Cancer Res, 2005 Feb 11; 11(2 Pt 1). PMID: 15701862
Highly Cited.
Distinct roles for CD28 and cytotoxic T lymphocyte-associated molecule-4 receptors during T cell activation?
P S Linsley.
J Exp Med, 1995 Aug 01; 182(2). PMID: 7543133    Free PMC article.
Review.
CTLA-4 regulates induction of anergy in vivo.
R J Greenwald, V A Boussiotis, +2 authors, A H Sharpe.
Immunity, 2001 Mar 10; 14(2). PMID: 11239447
Highly Cited.
CTLA-4 blockade in murine bone marrow chimeras induces a host-derived antileukemic effect without graft-versus-host disease.
S Fevery, A D Billiau, +10 authors, P Vandenberghe.
Leukemia, 2007 May 18; 21(7). PMID: 17508005
Activation of the NLRP3 inflammasome in dendritic cells induces IL-1beta-dependent adaptive immunity against tumors.
François Ghiringhelli, Lionel Apetoh, +23 authors, Laurence Zitvogel.
Nat Med, 2009 Sep 22; 15(10). PMID: 19767732
Highly Cited.
PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors.
Michael A Curran, Welby Montalvo, Hideo Yagita, James P Allison.
Proc Natl Acad Sci U S A, 2010 Feb 18; 107(9). PMID: 20160101    Free PMC article.
Highly Cited.
Cytotoxic T lymphocyte antigen-4 (CTLA-4) regulates primary and secondary peptide-specific CD4(+) T cell responses.
C A Chambers, M S Kuhns, J P Allison.
Proc Natl Acad Sci U S A, 1999 Jul 21; 96(15). PMID: 10411922    Free PMC article.
CTLA-4 can function as a negative regulator of T cell activation.
T L Walunas, D J Lenschow, +5 authors, J A Bluestone.
Immunity, 1994 Aug 01; 1(5). PMID: 7882171
Highly Cited.
Overcoming immunologic tolerance to melanoma: targeting CTLA-4 with ipilimumab (MDX-010).
Jeffrey Weber.
Oncologist, 2008 Nov 15; 13 Suppl 4. PMID: 19001147
Review.
Enhanced tumor eradication by combining CTLA-4 or PD-1 blockade with CpG therapy.
Sara M Mangsbo, Linda C Sandin, +3 authors, Thomas H Tötterman.
J Immunother, 2010 May 07; 33(3). PMID: 20445343
Two distinct pathways of immuno-modulation improve potency of p53 immunization in rejecting established tumors.
Pirouz Daftarian, Guang-Yun Song, +4 authors, Joshua D I Ellenhorn.
Cancer Res, 2004 Aug 04; 64(15). PMID: 15289349
Synergism of cytotoxic T lymphocyte-associated antigen 4 blockade and depletion of CD25(+) regulatory T cells in antitumor therapy reveals alternative pathways for suppression of autoreactive cytotoxic T lymphocyte responses.
R P Sutmuller, L M van Duivenvoorde, +6 authors, C J Melief.
J Exp Med, 2001 Sep 19; 194(6). PMID: 11560997    Free PMC article.
Highly Cited.
CD4+FoxP3+ regulatory T cells gradually accumulate in gliomas during tumor growth and efficiently suppress antiglioma immune responses in vivo.
Oliver M Grauer, Stefan Nierkens, +5 authors, Gosse J Adema.
Int J Cancer, 2007 Feb 23; 121(1). PMID: 17315190
Foxp3 in control of the regulatory T cell lineage.
Ye Zheng, Alexander Y Rudensky.
Nat Immunol, 2007 Apr 19; 8(5). PMID: 17440451
Highly Cited. Review.
Combination therapy of established tumors by antibodies targeting immune activating and suppressing molecules.
Kazuyoshi Takeda, Yuko Kojima, +7 authors, Mark J Smyth.
J Immunol, 2010 Apr 20; 184(10). PMID: 20400706
Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4.
P Waterhouse, J M Penninger, +6 authors, T W Mak.
Science, 1995 Nov 10; 270(5238). PMID: 7481803
Highly Cited.
The CD28 and CTLA-4 receptors associate with the serine/threonine phosphatase PP2A.
E Chuang, T S Fisher, +7 authors, C B Thompson.
Immunity, 2000 Oct 06; 13(3). PMID: 11021529
Immunogenic and tolerogenic cell death.
Douglas R Green, Thomas Ferguson, Laurence Zitvogel, Guido Kroemer.
Nat Rev Immunol, 2009 Apr 15; 9(5). PMID: 19365408    Free PMC article.
Highly Cited. Review.
Secondary but not primary T cell responses are enhanced in CTLA-4-deficient CD8+ T cells.
C A Chambers, T J Sullivan, T Truong, J P Allison.
Eur J Immunol, 1998 Nov 10; 28(10). PMID: 9808182
CTLA-4 control over Foxp3+ regulatory T cell function.
Kajsa Wing, Yasushi Onishi, +5 authors, Shimon Sakaguchi.
Science, 2008 Oct 11; 322(5899). PMID: 18845758
Highly Cited.
Elimination of residual metastatic prostate cancer after surgery and adjunctive cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) blockade immunotherapy.
E D Kwon, B A Foster, +4 authors, M B Burg.
Proc Natl Acad Sci U S A, 1999 Dec 28; 96(26). PMID: 10611340    Free PMC article.
Single dose of anti-CTLA-4 enhances CD8+ T-cell memory formation, function, and maintenance.
Virginia A Pedicord, Welby Montalvo, Ingrid M Leiner, James P Allison.
Proc Natl Acad Sci U S A, 2010 Dec 22; 108(1). PMID: 21173239    Free PMC article.
Systemic CTLA-4 blockade ameliorates glioma-induced changes to the CD4+ T cell compartment without affecting regulatory T-cell function.
Peter E Fecci, Hidenobu Ochiai, +7 authors, John H Sampson.
Clin Cancer Res, 2007 Apr 04; 13(7). PMID: 17404100
Highly Cited.
CTLA-4 blockade synergizes with tumor-derived granulocyte-macrophage colony-stimulating factor for treatment of an experimental mammary carcinoma.
A A Hurwitz, T F Yu, D R Leach, J P Allison.
Proc Natl Acad Sci U S A, 1998 Aug 26; 95(17). PMID: 9707601    Free PMC article.
Highly Cited.
Reversal of the TCR stop signal by CTLA-4.
Helga Schneider, Jos Downey, +7 authors, Christopher E Rudd.
Science, 2006 Aug 26; 313(5795). PMID: 16931720
Highly Cited.
The evolution of thalidomide and its IMiD derivatives as anticancer agents.
J Blake Bartlett, Keith Dredge, Angus G Dalgleish.
Nat Rev Cancer, 2004 Apr 02; 4(4). PMID: 15057291
Highly Cited. Review.
Cutting edge: a soluble form of CTLA-4 in patients with autoimmune thyroid disease.
M K Oaks, K M Hallett.
J Immunol, 2000 May 09; 164(10). PMID: 10799854
Combination therapy with anti-CTL antigen-4 and anti-4-1BB antibodies enhances cancer immunity and reduces autoimmunity.
Ergun Kocak, Kenneth Lute, +8 authors, Yang Liu.
Cancer Res, 2006 Jul 20; 66(14). PMID: 16849577
Realization of the therapeutic potential of CTLA-4 blockade in low-dose chemotherapy-treated tumor-bearing mice.
M B Mokyr, T Kalinichenko, L Gorelik, J A Bluestone.
Cancer Res, 1998 Dec 16; 58(23). PMID: 9850053
Regulation of surface and intracellular expression of CTLA4 on mouse T cells.
M L Alegre, P J Noel, +4 authors, C B Thompson.
J Immunol, 1996 Dec 01; 157(11). PMID: 8943377
Highly Cited.
Generation of antitumor immunity by cytotoxic T lymphocyte epitope peptide vaccination, CpG-oligodeoxynucleotide adjuvant, and CTLA-4 blockade.
Eduardo Davila, Richard Kennedy, Esteban Celis.
Cancer Res, 2003 Jun 18; 63(12). PMID: 12810660
The interaction properties of costimulatory molecules revisited.
Alison V Collins, Douglas W Brodie, +6 authors, Simon J Davis.
Immunity, 2002 Aug 28; 17(2). PMID: 12196291
Highly Cited.
Intranasal delivery of the cytoplasmic domain of CTLA-4 using a novel protein transduction domain prevents allergic inflammation.
Je-Min Choi, Mi-Hyun Ahn, +15 authors, Sang-Kyou Lee.
Nat Med, 2006 Apr 11; 12(5). PMID: 16604087
Negative regulators of T-cell activation: potential targets for therapeutic intervention in cancer, autoimmune disease, and persistent infections.
Tsvetelina Pentcheva-Hoang, Emily Corse, James P Allison.
Immunol Rev, 2009 May 12; 229(1). PMID: 19426215
Review.
CTLA-4 regulates cell cycle progression during a primary immune response.
Rebecca J Greenwald, Mariette A Oosterwegel, +4 authors, Arlene H Sharpe.
Eur J Immunol, 2002 Jan 25; 32(2). PMID: 11807776
CD28-mediated co-stimulation: a quantitative support for TCR signalling.
Oreste Acuto, Frédérique Michel.
Nat Rev Immunol, 2003 Dec 04; 3(12). PMID: 14647476
Highly Cited. Review.
Enhanced induction of antitumor T-cell responses by cytotoxic T lymphocyte-associated molecule-4 blockade: the effect is manifested only at the restricted tumor-bearing stages.
Y F Yang, J P Zou, +6 authors, T Hamaoka.
Cancer Res, 1997 Oct 27; 57(18). PMID: 9307290
CD28 induces immunostimulatory signals in dendritic cells via CD80 and CD86.
Ciriana Orabona, Ursula Grohmann, +9 authors, Paolo Puccetti.
Nat Immunol, 2004 Oct 07; 5(11). PMID: 15467723
CTLA-4 up-regulation of lymphocyte function-associated antigen 1 adhesion and clustering as an alternate basis for coreceptor function.
Helga Schneider, Elke Valk, +2 authors, Christopher E Rudd.
Proc Natl Acad Sci U S A, 2005 Aug 30; 102(36). PMID: 16126897    Free PMC article.
Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy.
Lionel Apetoh, François Ghiringhelli, +25 authors, Laurence Zitvogel.
Nat Med, 2007 Aug 21; 13(9). PMID: 17704786
Highly Cited.
Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria.
Jedd D Wolchok, Axel Hoos, +9 authors, F Stephen Hodi.
Clin Cancer Res, 2009 Nov 26; 15(23). PMID: 19934295
Highly Cited.
The effect of a therapeutic dendritic cell-based cancer vaccination depends on the blockage of CTLA-4 signaling.
Ozcan Met, Mingjun Wang, +3 authors, Mogens H Claesson.
Cancer Lett, 2006 Jan 10; 231(2). PMID: 16399226
Adenoviral vaccination combined with CD40 stimulation and CTLA-4 blockage can lead to complete tumor regression in a murine melanoma model.
Maria R Sorensen, Peter J Holst, +2 authors, Allan R Thomsen.
Vaccine, 2010 Aug 05; 28(41). PMID: 20682365
An autoimmune disease-associated CTLA-4 splice variant lacking the B7 binding domain signals negatively in T cells.
Lalitha Vijayakrishnan, Jacqueline M Slavik, +9 authors, Vijay K Kuchroo.
Immunity, 2004 May 15; 20(5). PMID: 15142525
CTLA-4: new insights into its biological function and use in tumor immunotherapy.
Jackson G Egen, Michael S Kuhns, James P Allison.
Nat Immunol, 2002 Jun 28; 3(7). PMID: 12087419
Highly Cited. Review.
CTLA-4 and PD-1 receptors inhibit T-cell activation by distinct mechanisms.
Richard V Parry, Jens M Chemnitz, +6 authors, James L Riley.
Mol Cell Biol, 2005 Oct 18; 25(21). PMID: 16227604    Free PMC article.
Highly Cited.
An immune-active tumor microenvironment favors clinical response to ipilimumab.
Rui-Ru Ji, Scott D Chasalow, +9 authors, Vafa Shahabi.
Cancer Immunol Immunother, 2011 Dec 08; 61(7). PMID: 22146893
Highly Cited.
Anti-CTLA-4 antibody therapy: immune monitoring during clinical development of a novel immunotherapy.
Margaret K Callahan, Jedd D Wolchok, James P Allison.
Semin Oncol, 2010 Nov 16; 37(5). PMID: 21074063    Free PMC article.
Review.
Overcoming immunologic tolerance to melanoma: targeting CTLA-4 with tremelimumab (CP-675,206).
Antoni Ribas.
Oncologist, 2008 Nov 15; 13 Suppl 4. PMID: 19001146
Review.
Engagement of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) induces transforming growth factor beta (TGF-beta) production by murine CD4(+) T cells.
W Chen, W Jin, S M Wahl.
J Exp Med, 1998 Nov 17; 188(10). PMID: 9815262    Free PMC article.
Potent induction of tumor immunity by combining tumor cryoablation with anti-CTLA-4 therapy.
Rebecca Waitz, Stephen B Solomon, +4 authors, James P Allison.
Cancer Res, 2011 Nov 24; 72(2). PMID: 22108823    Free PMC article.
B7-independent inhibition of T cells by CTLA-4.
Shunsuke Chikuma, Abul K Abbas, Jeffrey A Bluestone.
J Immunol, 2005 Jun 24; 175(1). PMID: 15972645
CTLA-4 blockade: therapeutic potential in cancer treatments.
Ahmad A Tarhini, Fatima Iqbal.
Onco Targets Ther, 2010 Jul 10; 3. PMID: 20616954    Free PMC article.
Inhibition of T cell proliferation by macrophage tryptophan catabolism.
D H Munn, E Shafizadeh, +3 authors, A L Mellor.
J Exp Med, 1999 May 04; 189(9). PMID: 10224276    Free PMC article.
Highly Cited.
Spatiotemporal basis of CTLA-4 costimulatory molecule-mediated negative regulation of T cell activation.
Tadashi Yokosuka, Wakana Kobayashi, +6 authors, Takashi Saito.
Immunity, 2010 Sep 28; 33(3). PMID: 20870175
Integrated NY-ESO-1 antibody and CD8+ T-cell responses correlate with clinical benefit in advanced melanoma patients treated with ipilimumab.
Jianda Yuan, Matthew Adamow, +16 authors, Sacha Gnjatic.
Proc Natl Acad Sci U S A, 2011 Sep 22; 108(40). PMID: 21933959    Free PMC article.
Highly Cited.
Functionally distinct LAG-3 and PD-1 subsets on activated and chronically stimulated CD8 T cells.
Joseph F Grosso, Monica V Goldberg, +7 authors, Charles G Drake.
J Immunol, 2009 May 21; 182(11). PMID: 19454660    Free PMC article.
Immune regulatory antibodies: are they the next advance?
Jedd D Wolchok, Arvin S Yang, Jeffrey S Weber.
Cancer J, 2010 Aug 10; 16(4). PMID: 20693841    Free PMC article.
Review.
Specific subsets of murine dendritic cells acquire potent T cell regulatory functions following CTLA4-mediated induction of indoleamine 2,3 dioxygenase.
Andrew L Mellor, Phillip Chandler, +7 authors, David H Munn.
Int Immunol, 2004 Sep 08; 16(10). PMID: 15351783
Blockade of CTLA-4 on both effector and regulatory T cell compartments contributes to the antitumor activity of anti-CTLA-4 antibodies.
Karl S Peggs, Sergio A Quezada, +2 authors, James P Allison.
J Exp Med, 2009 Jul 08; 206(8). PMID: 19581407    Free PMC article.
Highly Cited.
CD80 (B7-1) binds both CD28 and CTLA-4 with a low affinity and very fast kinetics.
P A van der Merwe, D L Bodian, +2 authors, S J Davis.
J Exp Med, 1997 Feb 03; 185(3). PMID: 9053440    Free PMC article.
Highly Cited.
Detailed analysis of immunologic effects of the cytotoxic T lymphocyte-associated antigen 4-blocking monoclonal antibody tremelimumab in peripheral blood of patients with melanoma.
Begoña Comin-Anduix, Yohan Lee, +13 authors, Antoni Ribas.
J Transl Med, 2008 May 03; 6. PMID: 18452610    Free PMC article.
CTLA-4 blockade increases IFNgamma-producing CD4+ICOShi cells to shift the ratio of effector to regulatory T cells in cancer patients.
Chrysoula I Liakou, Ashish Kamat, +5 authors, Padmanee Sharma.
Proc Natl Acad Sci U S A, 2008 Sep 27; 105(39). PMID: 18818309    Free PMC article.
Highly Cited.
CTLA-4 blockade reverses CD8+ T cell tolerance to tumor by a CD4+ T cell- and IL-2-dependent mechanism.
P Shrikant, A Khoruts, M F Mescher.
Immunity, 1999 Nov 05; 11(4). PMID: 10549630
Structural analysis of CTLA-4 function in vivo.
E L Masteller, E Chuang, +2 authors, C B Thompson.
J Immunol, 2000 May 09; 164(10). PMID: 10799894
Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4.
Omar S Qureshi, Yong Zheng, +12 authors, David M Sansom.
Science, 2011 Apr 09; 332(6029). PMID: 21474713    Free PMC article.
Highly Cited.
Induction of peripheral T cell tolerance in vivo requires CTLA-4 engagement.
V L Perez, L Van Parijs, +3 authors, A K Abbas.
Immunity, 1997 Apr 01; 6(4). PMID: 9133420
Highly Cited.
Modulation of tryptophan catabolism by regulatory T cells.
Francesca Fallarino, Ursula Grohmann, +7 authors, Paolo Puccetti.
Nat Immunol, 2003 Oct 28; 4(12). PMID: 14578884
Highly Cited.
A prospective phase II trial exploring the association between tumor microenvironment biomarkers and clinical activity of ipilimumab in advanced melanoma.
Omid Hamid, Henrik Schmidt, +9 authors, David Berman.
J Transl Med, 2011 Nov 30; 9. PMID: 22123319    Free PMC article.
Highly Cited.
Regulation of T cell receptor signaling by tyrosine phosphatase SYP association with CTLA-4.
L E Marengère, P Waterhouse, +3 authors, T W Mak.
Science, 1996 May 24; 272(5265). PMID: 8638161
Highly Cited.
The emerging role of CTLA-4 as an immune attenuator.
C B Thompson, J P Allison.
Immunity, 1997 Nov 14; 7(4). PMID: 9354465
Highly Cited. Review.
Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies.
Brian D Lehmann, Joshua A Bauer, +4 authors, Jennifer A Pietenpol.
J Clin Invest, 2011 Jun 03; 121(7). PMID: 21633166    Free PMC article.
Highly Cited.
Enhancement of antitumor immunity by CTLA-4 blockade.
D R Leach, M F Krummel, J P Allison.
Science, 1996 Mar 22; 271(5256). PMID: 8596936
Highly Cited.
Genetic evidence that the differential expression of the ligand-independent isoform of CTLA-4 is the molecular basis of the Idd5.1 type 1 diabetes region in nonobese diabetic mice.
Manabu Araki, Denise Chung, +11 authors, Linda S Wicker.
J Immunol, 2009 Sep 29; 183(8). PMID: 19783679    Free PMC article.
The metastasis-promoting roles of tumor-associated immune cells.
Heath A Smith, Yibin Kang.
J Mol Med (Berl), 2013 Mar 22; 91(4). PMID: 23515621    Free PMC article.
Highly Cited. Review.
At the bedside: CTLA-4- and PD-1-blocking antibodies in cancer immunotherapy.
Margaret K Callahan, Jedd D Wolchok.
J Leukoc Biol, 2013 May 15; 94(1). PMID: 23667165    Free PMC article.
Highly Cited. Review.
Locally advanced lung cancer: an optimal setting for vaccines and other immunotherapies.
Puneeth Iyengar, David E Gerber.
Cancer J, 2013 May 28; 19(3). PMID: 23708072    Free PMC article.
Review.
Synergy between chemotherapeutic agents and CTLA-4 blockade in preclinical tumor models.
Maria Jure-Kunkel, Gregg Masters, +4 authors, Rachel Humphrey.
Cancer Immunol Immunother, 2013 Jul 23; 62(9). PMID: 23873089    Free PMC article.
Making vaccines "on demand": a potential solution for emerging pathogens and biodefense?
Anne S De Groot, Leo Einck, +5 authors, William Martin.
Hum Vaccin Immunother, 2013 Jul 24; 9(9). PMID: 23877094    Free PMC article.
Review.
Ionizing radiation, ion transports, and radioresistance of cancer cells.
Stephan M Huber, Lena Butz, +4 authors, Franziska Eckert.
Front Physiol, 2013 Aug 24; 4. PMID: 23966948    Free PMC article.
Optimized and enhanced DNA plasmid vector based in vivo construction of a neutralizing anti-HIV-1 envelope glycoprotein Fab.
Kar Muthumani, Seleeke Flingai, +3 authors, David B Weiner.
Hum Vaccin Immunother, 2013 Sep 21; 9(10). PMID: 24045230    Free PMC article.
Intratumoral IL-12 combined with CTLA-4 blockade elicits T cell-mediated glioma rejection.
Johannes Vom Berg, Melissa Vrohlings, +5 authors, Burkhard Becher.
J Exp Med, 2013 Nov 28; 210(13). PMID: 24277150    Free PMC article.
Highly Cited.
Current advances in immunotherapy for pancreatic cancer.
Jennifer N Uram, Dung T Le.
Curr Probl Cancer, 2013 Dec 18; 37(5). PMID: 24331182    Free PMC article.
Review.
Clinical Implications of Co-Inhibitory Molecule Expression in the Tumor Microenvironment for DC Vaccination: A Game of Stop and Go.
Angela Vasaturo, Stefania Di Blasio, +4 authors, Stanleyson V Hato.
Front Immunol, 2013 Dec 19; 4. PMID: 24348481    Free PMC article.
Review.
Real-world impact of education: treating patients with ipilimumab in a community practice setting.
Blanca Ledezma, Annie Heng.
Cancer Manag Res, 2014 Jan 01; 6. PMID: 24379698    Free PMC article.
Review.
BRAF and MEK gene rearrangements in melanoma: implications for targeted therapy.
Pedro Madureira, Ramon Andrade de Mello.
Mol Diagn Ther, 2014 Jan 10; 18(3). PMID: 24403169
Review.
The promised land of human immunology.
Laura F Su, Arnold Han, +3 authors, Mark M Davis.
Cold Spring Harb Symp Quant Biol, 2014 Mar 19; 78. PMID: 24638855    Free PMC article.
[Advances in immunotherapies for non-small cell lung cancer].
Yuan He, Changxuan You.
Zhongguo Fei Ai Za Zhi, 2014 Mar 29; 17(3). PMID: 24667269    Free PMC article.
Review.
Radiotherapy-induced anti-tumor immunity contributes to the therapeutic efficacy of irradiation and can be augmented by CTLA-4 blockade in a mouse model.
Yuya Yoshimoto, Yoshiyuki Suzuki, +10 authors, Takashi Nakano.
PLoS One, 2014 Apr 02; 9(3). PMID: 24686897    Free PMC article.
Eomesodermin is required for antitumor immunity mediated by 4-1BB-agonist immunotherapy.
Chang Song, Kavitha Sadashivaiah, +3 authors, Arnob Banerjee.
Oncoimmunology, 2014 May 03; 3(1). PMID: 24790793    Free PMC article.
VISTA is a novel broad-spectrum negative checkpoint regulator for cancer immunotherapy.
J Louise Lines, Lorenzo F Sempere, +2 authors, Randolph Noelle.
Cancer Immunol Res, 2014 Jun 05; 2(6). PMID: 24894088    Free PMC article.
Highly Cited.
Immune checkpoint blockade in hepatocellular carcinoma: current progress and future directions.
Tai Hato, Lipika Goyal, +2 authors, Andrew X Zhu.
Hepatology, 2014 Jun 11; 60(5). PMID: 24912948    Free PMC article.
Highly Cited. Review.
Non-small-cell lung cancers: a heterogeneous set of diseases.
Zhao Chen, Christine M Fillmore, +2 authors, Kwok-Kin Wong.
Nat Rev Cancer, 2014 Jul 25; 14(8). PMID: 25056707    Free PMC article.
Highly Cited. Review.
Current issues in malignant pleural mesothelioma evaluation and management.
Jing Ai, James P Stevenson.
Oncologist, 2014 Jul 26; 19(9). PMID: 25061089    Free PMC article.
Manipulation of regulatory T cells and antigen-specific cytotoxic T lymphocyte-based tumour immunotherapy.
Shirin Karimi, Subhasis Chattopadhyay, Nitya G Chakraborty.
Immunology, 2014 Sep 23; 144(2). PMID: 25243729    Free PMC article.
Review.
Fusion of CTLA-4 with HPV16 E7 and E6 enhanced the potency of therapeutic HPV DNA vaccine.
Lili Gan, Rong Jia, +2 authors, Mingwen Fan.
PLoS One, 2014 Sep 30; 9(9). PMID: 25265018    Free PMC article.
64Cu-DOTA-anti-CTLA-4 mAb enabled PET visualization of CTLA-4 on the T-cell infiltrating tumor tissues.
Kei Higashikawa, Katsuharu Yagi, +4 authors, Shuichi Enomoto.
PLoS One, 2014 Nov 05; 9(11). PMID: 25365349    Free PMC article.
Non-viral immune electrogene therapy induces potent antitumour responses and has a curative effect in murine colon adenocarcinoma and melanoma cancer models.
P F Forde, L J Hall, +4 authors, D M Soden.
Gene Ther, 2014 Nov 07; 22(1). PMID: 25373914    Free PMC article.
Blocking monoclonal antibodies of TIM proteins as orchestrators of anti-tumor immune response.
Muhammad Baghdadi, Shintaro Takeuchi, Haruka Wada, Ken-Ichiro Seino.
MAbs, 2014 Dec 18; 6(5). PMID: 25517298    Free PMC article.
Review.
Cancer immunotherapy and breaking immune tolerance: new approaches to an old challenge.
Amani Makkouk, George J Weiner.
Cancer Res, 2014 Dec 20; 75(1). PMID: 25524899    Free PMC article.
Highly Cited. Review.
Developing biomarker-specific end points in lung cancer clinical trials.
Joel W Neal, Justin F Gainor, Alice T Shaw.
Nat Rev Clin Oncol, 2014 Dec 24; 12(3). PMID: 25533947
Review.
Diverse mechanisms regulate the surface expression of immunotherapeutic target ctla-4.
Helga Schneider, Christopher E Rudd.
Front Immunol, 2014 Dec 30; 5. PMID: 25538704    Free PMC article.
Review.
The CD28-B7 Family in Anti-Tumor Immunity: Emerging Concepts in Cancer Immunotherapy.
Joanne Leung, Woong-Kyung Suh.
Immune Netw, 2015 Jan 01; 14(6). PMID: 25550693    Free PMC article.
Review.
Three steps to breaking immune tolerance to lymphoma: a microparticle approach.
Amani Makkouk, Vijaya B Joshi, +5 authors, George J Weiner.
Cancer Immunol Res, 2015 Jan 30; 3(4). PMID: 25627654    Free PMC article.
CTLA-4 and PD-1 Pathway Blockade: Combinations in the Clinic.
Margaret K Callahan, Michael A Postow, Jedd D Wolchok.
Front Oncol, 2015 Feb 03; 4. PMID: 25642417    Free PMC article.
Highly Cited. Review.
The immune system in hepatocellular carcinoma and potential new immunotherapeutic strategies.
Gaetano Bertino, Shirin Demma, +9 authors, Michele Malaguarnera.
Biomed Res Int, 2015 Apr 22; 2015. PMID: 25893197    Free PMC article.
Review.
Cytotoxic T lymphocyte antigen 4 expression in human breast cancer: implications for prognosis.
Haiming Yu, Junlan Yang, +3 authors, Jiandong Wang.
Cancer Immunol Immunother, 2015 Apr 22; 64(7). PMID: 25893809    Free PMC article.
Tumor infiltrating lymphocytes in ovarian cancer.
Phillip P Santoiemma, Daniel J Powell.
Cancer Biol Ther, 2015 Apr 22; 16(6). PMID: 25894333    Free PMC article.
Highly Cited. Review.
Translational value of mouse models in oncology drug development.
Stephen E Gould, Melissa R Junttila, Frederic J de Sauvage.
Nat Med, 2015 May 08; 21(5). PMID: 25951530
Highly Cited.
Gene Expression Profiling and Pathway Network Analysis Predicts a Novel Antitumor Function for a Botanical-Derived Drug, PG2.
Yu-Lun Kuo, Chun-Houh Chen, +8 authors, Chi-Ying F Huang.
Evid Based Complement Alternat Med, 2015 May 15; 2015. PMID: 25972907    Free PMC article.
Immunomodulatory Drugs: Immune Checkpoint Agents in Acute Leukemia.
Hanna A Knaus, Christopher G Kanakry, Leo Luznik, Ivana Gojo.
Curr Drug Targets, 2015 May 20; 18(3). PMID: 25981611    Free PMC article.
Review.
Combination of Id2 Knockdown Whole Tumor Cells and Checkpoint Blockade: A Potent Vaccine Strategy in a Mouse Neuroblastoma Model.
Lina Chakrabarti, Clifford Morgan, Anthony D Sandler.
PLoS One, 2015 Jun 17; 10(6). PMID: 26079374    Free PMC article.
Network analysis of immunotherapy-induced regressing tumours identifies novel synergistic drug combinations.
W Joost Lesterhuis, Catherine Rinaldi, +8 authors, Richard A Lake.
Sci Rep, 2015 Jul 22; 5. PMID: 26193793    Free PMC article.
Immunotherapy of melanoma.
John B A G Haanen.
EJC Suppl, 2013 Sep 01; 11(2). PMID: 26217118    Free PMC article.
Review.
A multi-trimeric fusion of CD40L and gp100 tumor antigen activates dendritic cells and enhances survival in a B16-F10 melanoma DNA vaccine model.
Sachin Gupta, James M Termini, +5 authors, Geoffrey W Stone.
Vaccine, 2015 Aug 05; 33(38). PMID: 26241951    Free PMC article.
Intellectual property issues of immune checkpoint inhibitors.
Ulrich Storz.
MAbs, 2015 Oct 16; 8(1). PMID: 26466763    Free PMC article.
Radio-Immunotherapy-Induced Immunogenic Cancer Cells as Basis for Induction of Systemic Anti-Tumor Immune Responses - Pre-Clinical Evidence and Ongoing Clinical Applications.
Anja Derer, Lisa Deloch, +3 authors, Udo S Gaipl.
Front Immunol, 2015 Oct 27; 6. PMID: 26500646    Free PMC article.
Review.
Immunotherapy for non-small cell lung cancer: current concepts and clinical trials.
Marissa Mayor, Neng Yang, +2 authors, Prasad S Adusumilli.
Eur J Cardiothorac Surg, 2015 Oct 31; 49(5). PMID: 26516195    Free PMC article.
Review.
Construction of CTLA-4-Ig Fusion Gene in pBudCE4.1 Expression Vector.
Mahsa Yazdanpanah-Samani, Elham Mahmoudi Maymand, Tayebeh Jahangeerfam, Abbas Ghaderi.
Avicenna J Med Biotechnol, 2015 Nov 26; 7(4). PMID: 26605013    Free PMC article.
Emerging therapeutic targets in metastatic progression: A focus on breast cancer.
Zhuo Li, Yibin Kang.
Pharmacol Ther, 2016 Mar 24; 161. PMID: 27000769    Free PMC article.
Review.
Cytotoxic T lymphocyte antigen-4 expression in esophageal carcinoma: implications for prognosis.
Xiao-Fei Zhang, Ke Pan, +9 authors, Jian-Chuan Xia.
Oncotarget, 2016 Apr 07; 7(18). PMID: 27050369    Free PMC article.
Overcoming Hypoxia-Mediated Tumor Progression: Combinatorial Approaches Targeting pH Regulation, Angiogenesis and Immune Dysfunction.
Paul C McDonald, Shawn C Chafe, Shoukat Dedhar.
Front Cell Dev Biol, 2016 Apr 12; 4. PMID: 27066484    Free PMC article.
Review.
Cancer immunotherapy: the beginning of the end of cancer?
Sofia Farkona, Eleftherios P Diamandis, Ivan M Blasutig.
BMC Med, 2016 May 07; 14. PMID: 27151159    Free PMC article.
Highly Cited. Review.
SCIB2, an antibody DNA vaccine encoding NY-ESO-1 epitopes, induces potent antitumor immunity which is further enhanced by checkpoint blockade.
Wei Xue, Rachael L Metheringham, +5 authors, Lindy G Durrant.
Oncoimmunology, 2016 Jul 30; 5(6). PMID: 27471648    Free PMC article.
Progress in systemic therapy of advanced hepatocellular carcinoma.
Xin-Lei Gong, Shu-Kui Qin.
World J Gastroenterol, 2016 Aug 23; 22(29). PMID: 27547002    Free PMC article.
Review.
Immune checkpoint inhibitors: the new frontier in non-small-cell lung cancer treatment.
Hazem El-Osta, Kamran Shahid, Glenn M Mills, Prakash Peddi.
Onco Targets Ther, 2016 Aug 31; 9. PMID: 27574451    Free PMC article.
Review.
Preclinical Development of Ipilimumab and Nivolumab Combination Immunotherapy: Mouse Tumor Models, In Vitro Functional Studies, and Cynomolgus Macaque Toxicology.
Mark J Selby, John J Engelhardt, +11 authors, Alan J Korman.
PLoS One, 2016 Sep 10; 11(9). PMID: 27610613    Free PMC article.
Highly Cited.
Phenotypic screening reveals TNFR2 as a promising target for cancer immunotherapy.
Geoffrey S Williams, Bina Mistry, +20 authors, Robert W Wilkinson.
Oncotarget, 2016 Sep 15; 7(42). PMID: 27626702    Free PMC article.
Manipulation of Regulatory Cells' Responses to Treatments for Chronic Hepatitis B Virus Infection.
Soheil Tavakolpour, Seyed Moayed Alavian, Shahnaz Sali.
Hepat Mon, 2016 Sep 16; 16(6). PMID: 27630728    Free PMC article.
Programmed death-ligand 1 expression in gastric adenocarcinoma is a poor prognostic factor in a high CD8+ tumor infiltrating lymphocytes group.
Hyeyoon Chang, Woon Yong Jung, +5 authors, Baek-Hui Kim.
Oncotarget, 2016 Oct 16; 7(49). PMID: 27741514    Free PMC article.
Osteosarcoma Overview.
Brock A Lindsey, Justin E Markel, Eugenie S Kleinerman.
Rheumatol Ther, 2016 Dec 10; 4(1). PMID: 27933467    Free PMC article.
Highly Cited. Review.
Potent CD4+ T cell-associated antitumor memory responses induced by trifunctional bispecific antibodies in combination with immune checkpoint inhibition.
Nina Deppisch, Peter Ruf, +2 authors, Ralph Mocikat.
Oncotarget, 2016 Dec 15; 8(3). PMID: 27966460    Free PMC article.
Impact of CTLA-4 blockade in conjunction with metronomic chemotherapy on preclinical breast cancer growth.
Karla Parra, Paloma Valenzuela, +10 authors, Giulio Francia.
Br J Cancer, 2017 Jan 06; 116(3). PMID: 28056464    Free PMC article.
Dynamic versus static biomarkers in cancer immune checkpoint blockade: unravelling complexity.
W Joost Lesterhuis, Anthony Bosco, +3 authors, Richard A Lake.
Nat Rev Drug Discov, 2017 Jan 07; 16(4). PMID: 28057932
Highly Cited. Review.
Immunotherapy: incorporation in the evolving paradigm of renal cancer management and future prospects.
Kenneth G Liu, Sorab Gupta, Sanjay Goel.
Oncotarget, 2017 Jan 07; 8(10). PMID: 28061473    Free PMC article.
Review.
Clinical Implications of Cytotoxic T Lymphocyte Antigen-4 Expression on Tumor Cells and Tumor-Infiltrating Lymphocytes in Extrahepatic Bile Duct Cancer Patients Undergoing Surgery Plus Adjuvant Chemoradiotherapy.
Yu Jin Lim, Jaemoon Koh, +7 authors, Yung-Jue Bang.
Target Oncol, 2017 Jan 14; 12(2). PMID: 28084572
Replication Study: The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors.
Stephen K Horrigan, Reproducibility Project: Cancer Biology.
Elife, 2017 Jan 20; 6. PMID: 28100392    Free PMC article.
Increased CTLA-4+ T cells may contribute to impaired T helper type 1 immune responses in patients with chronic obstructive pulmonary disease.
Dino B A Tan, Teck-Hui Teo, +5 authors, Yuben P Moodley.
Immunology, 2017 Feb 13; 151(2). PMID: 28190271    Free PMC article.
The prognostic value of cytotoxic T-lymphocyte antigen 4 in cancers: a systematic review and meta-analysis.
Pingping Hu, Qiqi Liu, +4 authors, Jiandong Zhang.
Sci Rep, 2017 Feb 18; 7. PMID: 28211499    Free PMC article.
Systematic Review.
Combining talimogene laherparepvec with immunotherapies in melanoma and other solid tumors.
Reinhard Dummer, Christoph Hoeller, Isabella Pezzani Gruter, Olivier Michielin.
Cancer Immunol Immunother, 2017 Feb 27; 66(6). PMID: 28238174    Free PMC article.
Review.
Priming is key to effective incorporation of image-guided thermal ablation into immunotherapy protocols.
Matthew T Silvestrini, Elizabeth S Ingham, +12 authors, Katherine W Ferrara.
JCI Insight, 2017 Mar 30; 2(6). PMID: 28352658    Free PMC article.
Anti-angiogenesis for cancer revisited: Is there a role for combinations with immunotherapy?
Rakesh R Ramjiawan, Arjan W Griffioen, Dan G Duda.
Angiogenesis, 2017 Apr 01; 20(2). PMID: 28361267    Free PMC article.
Highly Cited. Review.
Increased Expression of Cytotoxic T-Lymphocyte-Associated Protein 4 by T Cells, Induced by B7 in Sera, Reduces Adaptive Immunity in Patients With Acute Liver Failure.
Wafa Khamri, Robin D Abeles, +17 authors, Charalambos G Antoniades.
Gastroenterology, 2017 Apr 02; 153(1). PMID: 28363639    Free PMC article.
Humanized Mice with Subcutaneous Human Solid Tumors for Immune Response Analysis of Vaccinia Virus-Mediated Oncolysis.
Desislava Tsoneva, Boris Minev, +3 authors, Aladar A Szalay.
Mol Ther Oncolytics, 2017 May 10; 5. PMID: 28480327    Free PMC article.
Efficient Generation of Bispecific Murine Antibodies for Pre-Clinical Investigations in Syngeneic Rodent Models.
Aran F Labrijn, Joyce I Meesters, +8 authors, Paul W H I Parren.
Sci Rep, 2017 Jun 01; 7(1). PMID: 28559564    Free PMC article.
Epi-drugs in combination with immunotherapy: a new avenue to improve anticancer efficacy.
Roberta Mazzone, Clemens Zwergel, Antonello Mai, Sergio Valente.
Clin Epigenetics, 2017 Jun 03; 9. PMID: 28572863    Free PMC article.
Highly Cited. Review.
Basal cell carcinoma pathogenesis and therapy involving hedgehog signaling and beyond.
Anshika Bakshi, Sandeep C Chaudhary, +2 authors, Mohammad Athar.
Mol Carcinog, 2017 Jun 03; 56(12). PMID: 28574612    Free PMC article.
Review.
Intratumoral FoxP3+Helios+ Regulatory T Cells Upregulating Immunosuppressive Molecules Are Expanded in Human Colorectal Cancer.
Azharuddin Sajid Syed Khaja, Salman M Toor, +2 authors, Eyad Elkord.
Front Immunol, 2017 Jun 13; 8. PMID: 28603527    Free PMC article.
A Novel Unsupervised Algorithm for Biological Process-based Analysis on Cancer.
Tianci Song, Sha Cao, +3 authors, Yanchun Liang.
Sci Rep, 2017 Jul 07; 7(1). PMID: 28680165    Free PMC article.
Systemic treatment of hepatocellular carcinoma: Past, present and future.
Esther Una Cidon.
World J Hepatol, 2017 Jul 15; 9(18). PMID: 28706578    Free PMC article.
Review.
Immunotherapy for malignant pleural mesothelioma: current status and future directions.
Jordan Dozier, Hua Zheng, Prasad S Adusumilli.
Transl Lung Cancer Res, 2017 Jul 18; 6(3). PMID: 28713676    Free PMC article.
Review.
Cell genomics and immunosuppressive biomarker expression influence PD-L1 immunotherapy treatment responses in HNSCC-a computational study.
Amber M Bates, Emily A Lanzel, +3 authors, Kim A Brogden.
Oral Surg Oral Med Oral Pathol Oral Radiol, 2017 Aug 02; 124(2). PMID: 28756882    Free PMC article.
Chemotherapy for hepatocellular carcinoma: The present and the future.
Marco Le Grazie, Maria Rosa Biagini, +2 authors, Andrea Galli.
World J Hepatol, 2017 Aug 22; 9(21). PMID: 28824742    Free PMC article.
Highly Cited. Review.
Genomic Landscape of Atypical Adenomatous Hyperplasia Reveals Divergent Modes to Lung Adenocarcinoma.
Smruthy Sivakumar, F Anthony San Lucas, +14 authors, Humam Kadara.
Cancer Res, 2017 Sep 28; 77(22). PMID: 28951454    Free PMC article.
Production and Evaluation of Specific Single-Chain Antibodies against CTLA-4 for Cancer-Targeted Therapy.
Farideh Hosseinzadeh, Saeed Mohammadi, Foroogh Nejatollahi.
Rep Biochem Mol Biol, 2017 Nov 02; 6(1). PMID: 29090224    Free PMC article.
Dendritic cell therapy in melanoma.
Carmen Alvarez-Dominguez, Ricardo Calderón-Gonzalez, +5 authors, Fernando Rivera.
Ann Transl Med, 2017 Nov 09; 5(19). PMID: 29114544    Free PMC article.
Review.
Immunotherapy and gene therapy as novel treatments for cancer.
Martha Montserrat Rangel-Sosa, Estuardo Aguilar-Córdova, Augusto Rojas-Martínez.
Colomb Med (Cali), 2017 Dec 08; 48(3). PMID: 29213157    Free PMC article.
Review.
Interleukin-21 combined with PD-1 or CTLA-4 blockade enhances antitumor immunity in mouse tumor models.
Katherine E Lewis, Mark J Selby, +11 authors, Stacey R Dillon.
Oncoimmunology, 2018 Jan 04; 7(1). PMID: 29296539    Free PMC article.
The synergistic antitumor effect of arsenic trioxide combined with cytotoxic T cells in pulmonary metastasis model of colon cancer.
Lei Wang, Wentao Liang, +3 authors, Zhong Liu.
Oncotarget, 2018 Jan 10; 8(65). PMID: 29312633    Free PMC article.
HDAC inhibition potentiates immunotherapy in triple negative breast cancer.
Manuela Terranova-Barberio, Scott Thomas, +6 authors, Pamela N Munster.
Oncotarget, 2018 Jan 27; 8(69). PMID: 29371976    Free PMC article.
Highly Cited.
Electrotransfer of Different Control Plasmids Elicits Different Antitumor Effectiveness in B16.F10 Melanoma.
Masa Bosnjak, Tanja Jesenko, +4 authors, Maja Cemazar.
Cancers (Basel), 2018 Feb 01; 10(2). PMID: 29382170    Free PMC article.
Modeling Human Antitumor Responses In Vivo Using Umbilical Cord Blood-Engrafted Mice.
Nicholas A Zumwalde, Jenny E Gumperz.
Front Immunol, 2018 Feb 13; 9. PMID: 29434589    Free PMC article.
Review.
Genomics of NSCLC patients both affirm PD-L1 expression and predict their clinical responses to anti-PD-1 immunotherapy.
Kim A Brogden, Deepak Parashar, +8 authors, Shireen Vali.
BMC Cancer, 2018 Mar 01; 18(1). PMID: 29486723    Free PMC article.
Optimizing Tumor Microenvironment for Cancer Immunotherapy: β-Glucan-Based Nanoparticles.
Mei Zhang, Julian A Kim, Alex Yee-Chen Huang.
Front Immunol, 2018 Mar 15; 9. PMID: 29535722    Free PMC article.
Review.
Cytotoxic T lymphocyte associated antigen 4 expression predicts poor prognosis in luminal B HER2-negative breast cancer.
Gaochen Lan, Jie Li, +4 authors, Xi Chen.
Oncol Lett, 2018 Mar 20; 15(4). PMID: 29552143    Free PMC article.
Structure-function analysis and therapeutic efficacy of antibodies to fungal melanin for melanoma radioimmunotherapy.
J D Nosanchuk, A Jeyakumar, +14 authors, E Dadachova.
Sci Rep, 2018 Apr 05; 8(1). PMID: 29615812    Free PMC article.
Toxicological and pharmacological assessment of AGEN1884, a novel human IgG1 anti-CTLA-4 antibody.
Randi B Gombos, Ana Gonzalez, +24 authors, Nicholas S Wilson.
PLoS One, 2018 Apr 05; 13(4). PMID: 29617360    Free PMC article.
Increased vessel perfusion predicts the efficacy of immune checkpoint blockade.
Xichen Zheng, Zhaoxu Fang, +17 authors, Yuhui Huang.
J Clin Invest, 2018 Apr 18; 128(5). PMID: 29664018    Free PMC article.
Novel Immunotherapeutics for the Treatment of Glioblastoma: The Last Decade of Research.
Emaad M Khansur, Ashish H Shah, +2 authors, Ricardo J Komotar.
Cureus, 2018 Apr 26; 10(1). PMID: 29692957    Free PMC article.
Review.
T Cell Calcium Signaling Regulation by the Co-Receptor CD5.
Claudia M Tellez Freitas, Deborah K Johnson, K Scott Weber.
Int J Mol Sci, 2018 Apr 28; 19(5). PMID: 29701673    Free PMC article.
Review.
A mathematical modelling tool for unravelling the antibody-mediated effects on CTLA-4 interactions.
Aravindhan Ganesan, Theinmozhi Arulraj, Tahir Choulli, Khaled H Barakat.
BMC Med Inform Decis Mak, 2018 Jun 13; 18(1). PMID: 29890992    Free PMC article.
Recent advances on T-cell exhaustion in malaria infection.
Esaki M Shankar, R Vignesh, A P Dash.
Med Microbiol Immunol, 2018 Jun 25; 207(3-4). PMID: 29936565
Review.
Reversal of indoleamine 2,3-dioxygenase-mediated cancer immune suppression by systemic kynurenine depletion with a therapeutic enzyme.
Todd A Triplett, Kendra C Garrison, +23 authors, George Georgiou.
Nat Biotechnol, 2018 Jul 17; 36(8). PMID: 30010674    Free PMC article.
Checkpoint blockade-based immunotherapy in the context of tumor microenvironment: Opportunities and challenges.
Jingjing Duan, Yu Wang, Shunchang Jiao.
Cancer Med, 2018 Aug 09; 7(9). PMID: 30088347    Free PMC article.
Review.
Early Investigations and Recent Advances in Intraperitoneal Immunotherapy for Peritoneal Metastasis.
Anusha Thadi, Marian Khalili, +3 authors, Wilbur B Bowne.
Vaccines (Basel), 2018 Aug 15; 6(3). PMID: 30103457    Free PMC article.
Review.
Abscopal effect of radiotherapy combined with immune checkpoint inhibitors.
Yang Liu, Yinping Dong, +3 authors, Jinming Yu.
J Hematol Oncol, 2018 Aug 18; 11(1). PMID: 30115069    Free PMC article.
Highly Cited. Review.
Endocrine Toxicity of Cancer Immunotherapy Targeting Immune Checkpoints.
Lee-Shing Chang, Romualdo Barroso-Sousa, +3 authors, Le Min.
Endocr Rev, 2018 Sep 06; 40(1). PMID: 30184160    Free PMC article.
Review.
Adjuvant treatment for stage III melanoma in the era of targeted medicine and immunotherapy.
Eytan Ben-Ami, Jacob Schachter.
Melanoma Manag, 2016 Jun 01; 3(2). PMID: 30190882    Free PMC article.
Review.
Emerging ways to treat breast cancer: will promises be met?
Pouria Samadi, Sahar Saki, +2 authors, Massoud Saidijam.
Cell Oncol (Dordr), 2018 Sep 28; 41(6). PMID: 30259416
Review.
Checkpoint inhibitor use in two heart transplant patients with metastatic melanoma and review of high-risk populations.
Michael J Grant, Nicholas DeVito, April K S Salama.
Melanoma Manag, 2018 Nov 22; 5(4). PMID: 30459942    Free PMC article.
Review.
Radiation as an In Situ Auto-Vaccination: Current Perspectives and Challenges.
Taichiro Goto.
Vaccines (Basel), 2019 Aug 29; 7(3). PMID: 31455032    Free PMC article.
Review.
Preclinical rationale and clinical efficacy of antiangiogenic therapy and immune checkpoint blockade combination therapy in urogenital tumors.
Ning Zhu, Shanshan Weng, +4 authors, Ying Yuan.
J Cancer Res Clin Oncol, 2019 Oct 17; 145(12). PMID: 31617075
Review.
Dexamethasone differentially depletes tumour and peripheral blood lymphocytes and can impact the efficacy of chemotherapy/checkpoint blockade combination treatment.
Wayne J Aston, Danika E Hope, +5 authors, W Joost Lesterhuis.
Oncoimmunology, 2019 Oct 28; 8(11). PMID: 31646089    Free PMC article.
T Regulatory Cells and Priming the Suppressive Tumor Microenvironment.
Christina M Paluskievicz, Xuefang Cao, +3 authors, Jonathan S Bromberg.
Front Immunol, 2019 Nov 05; 10. PMID: 31681327    Free PMC article.
Review.
Comparison of the molecular and cellular phenotypes of common mouse syngeneic models with human tumors.
Wenyan Zhong, Jeremy S Myers, +11 authors, Paul A Rejto.
BMC Genomics, 2020 Jan 04; 21(1). PMID: 31898484    Free PMC article.
Insights in the immunobiology of glioblastoma.
Dimitrios Strepkos, Mariam Markouli, +2 authors, Athanasios G Papavassiliou.
J Mol Med (Berl), 2019 Oct 28; 98(1). PMID: 31650201
Review.
Amplifying Outcomes: Checkpoint Inhibitor Combinations in First-Line Non-Small Cell Lung Cancer.
Barbara Melosky, Rosalyn Juergens, +5 authors, Quincy Chu.
Oncologist, 2019 May 30; 25(1). PMID: 31138727    Free PMC article.
A Triple Co-Delivery Liposomal Carrier That Enhances Apoptosis via an Intrinsic Pathway in Melanoma Cells.
Nina Filipczak, Anna Jaromin, +4 authors, Jerzy Gubernator.
Cancers (Basel), 2019 Dec 15; 11(12). PMID: 31835393    Free PMC article.
Sensitizing the Tumor Microenvironment to Immune Checkpoint Therapy.
Rachael M Zemek, Wee Loong Chin, +3 authors, W Joost Lesterhuis.
Front Immunol, 2020 Mar 07; 11. PMID: 32133005    Free PMC article.
Review.
Tumour cell-intrinsic CTLA4 regulates PD-L1 expression in non-small cell lung cancer.
Huijun Zhang, Pranabananda Dutta, +4 authors, Jinghong Li.
J Cell Mol Med, 2018 Nov 01; 23(1). PMID: 30378264    Free PMC article.
Tumor-conditional anti-CTLA4 uncouples antitumor efficacy from immunotherapy-related toxicity.
Chien-Chun Steven Pai, Donald M Simons, +22 authors, Lawrence Fong.
J Clin Invest, 2018 Dec 12; 129(1). PMID: 30530991    Free PMC article.
A Syngeneic ErbB2 Mammary Cancer Model for Preclinical Immunotherapy Trials.
Zsófia Pénzváltó, Jane Qian Chen, +5 authors, Alexander D Borowsky.
J Mammary Gland Biol Neoplasia, 2019 Feb 28; 24(2). PMID: 30810966    Free PMC article.
Targeted antibody and cytokine cancer immunotherapies through collagen affinity.
Jun Ishihara, Ako Ishihara, +15 authors, Jeffrey A Hubbell.
Sci Transl Med, 2019 Apr 12; 11(487). PMID: 30971453    Free PMC article.
Highly Cited.
Interaction of CD99 and its ligand upregulates IL-6 and TNF-α upon T cell activation.
Nuchjira Takheaw, Papawadee Earwong, +2 authors, Watchara Kasinrerk.
PLoS One, 2019 May 24; 14(5). PMID: 31120992    Free PMC article.
The multifaceted Foxp3fgfp allele enhances spontaneous and therapeutic immune surveillance of cancer in mice.
José Almeida-Santos, Marie-Louise Bergman, +3 authors, Jocelyne Demengeot.
Eur J Immunol, 2019 Nov 16; 50(3). PMID: 31729760    Free PMC article.
9th annual European Antibody Congress, November 11-13, 2013, Geneva, Switzerland.
Janice M Reichert, Alain Beck, +3 authors, Randall J Brezski.
MAbs, 2014 Feb 05; 6(2). PMID: 24492298    Free PMC article.
A guide to cancer immunotherapy: from T cell basic science to clinical practice.
Alex D Waldman, Jill M Fritz, Michael J Lenardo.
Nat Rev Immunol, 2020 May 21; 20(11). PMID: 32433532    Free PMC article.
Review.
Tumor progression locus 2 (TPL2) in tumor-promoting Inflammation, Tumorigenesis and Tumor Immunity.
Lucy Wanjiru Njunge, Andreanne Poppy Estania, +2 authors, Li Yang.
Theranostics, 2020 Jul 30; 10(18). PMID: 32724474    Free PMC article.
Review.
Scientifically based combination therapies with immuno-oncology checkpoint inhibitors.
Hui Yi Chew, Riccardo Dolcetti, Fiona Simpson.
Br J Clin Pharmacol, 2020 May 07; 86(9). PMID: 32372470    Free PMC article.
Review.
Advanced biomaterials for cancer immunotherapy.
Fan Yang, Kun Shi, +3 authors, Zhi-Yong Qian.
Acta Pharmacol Sin, 2020 Mar 04; 41(7). PMID: 32123302    Free PMC article.
Review.
The role and therapeutic implications of T cells in cancer of the lung.
Samuel C Neeve, Bruce Ws Robinson, Vanessa S Fear.
Clin Transl Immunology, 2019 Sep 06; 8(8). PMID: 31485330    Free PMC article.
The New Immunotherapy Combinations in the Treatment of Advanced Non-Small Cell Lung Cancer: Reality and Perspectives.
Danilo Rocco, Luigi D Gravara, Cesare Gridelli.
Curr Clin Pharmacol, 2019 Aug 11; 15(1). PMID: 31400270    Free PMC article.
Review.
Expression of immune checkpoints and T cell exhaustion markers in early and advanced stages of colorectal cancer.
Reem Saleh, Rowaida Z Taha, +7 authors, Eyad Elkord.
Cancer Immunol Immunother, 2020 May 13; 69(10). PMID: 32393998    Free PMC article.
Prolonging Survival: The Role of Immune Checkpoint Inhibitors in the Treatment of Extensive-Stage Small Cell Lung Cancer.
Barbara Melosky, Parneet K Cheema, +8 authors, Quincy Chu.
Oncologist, 2020 Aug 30; 25(11). PMID: 32860288    Free PMC article.
Review.
MRPL13 is a Prognostic Cancer Biomarker and Correlates with Immune Infiltrates in Breast Cancer.
Zuo Tao, Huandan Suo, +7 authors, Bo Chen.
Onco Targets Ther, 2020 Dec 05; 13. PMID: 33273831    Free PMC article.
Activating the Antitumor Immune Response in Non-Hodgkin Lymphoma Using Immune Checkpoint Inhibitors.
Maansi Joshi, Stephen M Ansell.
J Immunol Res, 2020 Dec 10; 2020. PMID: 33294467    Free PMC article.
Review.
Stimulation of an anti-tumor immune response with "chromatin-damaging" therapy.
Minhui Chen, Craig M Brackett, +8 authors, Katerina V Gurova.
Cancer Immunol Immunother, 2021 Jan 14; 70(7). PMID: 33439292    Free PMC article.
Anti-NKG2D single domain-based antibodies for the modulation of anti-tumor immune response.
Adeline Raynaud, Klervi Desrumeaux, +5 authors, Brigitte Kerfelec.
Oncoimmunology, 2021 Jan 19; 10(1). PMID: 33457075    Free PMC article.
Recent Advances in Monoclonal Antibody Therapy for Colorectal Cancers.
Kyusang Hwang, Jin Hwan Yoon, Ji Hyun Lee, Sukmook Lee.
Biomedicines, 2021 Jan 21; 9(1). PMID: 33466394    Free PMC article.
Review.
Therapy of lymphoma by immune checkpoint inhibitors: the role of T cells, NK cells and cytokine-induced tumor senescence.
Fatima Ahmetlic, Josia Fauser, +8 authors, Ralph Mocikat.
J Immunother Cancer, 2021 Jan 15; 9(1). PMID: 33441389    Free PMC article.
Immune checkpoint: The novel target for antitumor therapy.
Xianghu Jiang, Guohong Liu, Yirong Li, Yunbao Pan.
Genes Dis, 2019 Dec 20; 8(1). PMID: 33569511    Free PMC article.
Review.
Current methods in translational cancer research.
Michael W Lee, Mihailo Miljanic, +4 authors, Anna Capasso.
Cancer Metastasis Rev, 2020 Sep 16; 40(1). PMID: 32929562    Free PMC article.
Review.
Protective low-avidity anti-tumour CD8+ T cells are selectively attenuated by regulatory T cells.
Gessa Sugiyarto, David Prossor, +3 authors, Edward James.
Immunother Adv, 2021 Mar 23; 1(1). PMID: 33748824    Free PMC article.
The role of dendritic cells for therapy of B-cell lymphoma with immune checkpoint inhibitors.
Anne Scheuerpflug, Fatima Ahmetlić, +3 authors, Ralph Mocikat.
Cancer Immunol Immunother, 2020 Nov 04; 70(5). PMID: 33141285    Free PMC article.
Prognostic value of LRRC4C in Colon and Gastric Cancers correlates with Tumour Microenvironment Immunity.
XiaoFeng Yang, Purun Lei, +3 authors, HongBo Wei.
Int J Biol Sci, 2021 Apr 20; 17(5). PMID: 33867855    Free PMC article.
Natural Killer Cells and Regulatory T Cells Cross Talk in Hepatocellular Carcinoma: Exploring Therapeutic Options for the Next Decade.
Amber G Bozward, Frazer Warricker, Ye H Oo, Salim I Khakoo.
Front Immunol, 2021 May 18; 12. PMID: 33995362    Free PMC article.
Review.
Local and Targeted Delivery of Immune Checkpoint Blockade Therapeutics.
Xiao Han, Hongjun Li, +2 authors, Zhen Gu.
Acc Chem Res, 2020 Oct 20; 53(11). PMID: 33073988    Free PMC article.
Immune checkpoints in targeted-immunotherapy of pancreatic cancer: New hope for clinical development.
Seyed Hossein Kiaie, Mohammad Javad Sanaei, +5 authors, Behzad Baradaran.
Acta Pharm Sin B, 2021 Jun 08; 11(5). PMID: 34094821    Free PMC article.
Review.
Immune checkpoint blockade impairs immunosuppressive mechanisms of regulatory T cells in B-cell lymphoma.
Vera Bauer, Fatima Ahmetlić, +3 authors, Ralph Mocikat.
Transl Oncol, 2021 Jul 07; 14(9). PMID: 34229208    Free PMC article.
The KrasG12D;Trp53fl/fl murine model of undifferentiated pleomorphic sarcoma is macrophage dense, lymphocyte poor, and resistant to immune checkpoint blockade.
Karys M Hildebrand, Arvind K Singla, +9 authors, Michael J Monument.
PLoS One, 2021 Jul 10; 16(7). PMID: 34242269    Free PMC article.
Local Destruction of Tumors and Systemic Immune Effects.
Karl-Göran Tranberg.
Front Oncol, 2021 Jul 27; 11. PMID: 34307177    Free PMC article.
Review.
Epitranscriptomic Approach: To Improve the Efficacy of ICB Therapy by Co-Targeting Intracellular Checkpoint CISH.
Sunil Kumar, Parth Sarthi, +4 authors, Yong-Soo Bae.
Cells, 2021 Sep 29; 10(9). PMID: 34571899    Free PMC article.
Review.
Type I Interferon Promotes Antitumor T Cell Response in CRPC by Regulating MDSC.
Lilv Fan, Guiliang Xu, +8 authors, Xuanming Yang.
Cancers (Basel), 2021 Nov 14; 13(21). PMID: 34771735    Free PMC article.
Tumor membrane-based vaccine immunotherapy in combination with anti-CTLA-4 antibody confers protection against immune checkpoint resistant murine triple-negative breast cancer.
Christopher D Pack, Ramireddy Bommireddy, +9 authors, Periasamy Selvaraj.
Hum Vaccin Immunother, 2020 Jun 13; 16(12). PMID: 32530786    Free PMC article.
Identification of the Immune Cell Infiltration Landscape in Hepatocellular Carcinoma to Predict Prognosis and Guide Immunotherapy.
Shiyan Yang, Yajun Cheng, +3 authors, Shanzhong Tan.
Front Genet, 2021 Dec 14; 12. PMID: 34899862    Free PMC article.
Using a Prime-Boost Vaccination Strategy That Proved Effective for High Resolution Epitope Mapping to Characterize the Elusive Immunogenicity of Survivin.
Robert C Mould, Jacob P van Vloten, +9 authors, Byram W Bridle.
Cancers (Basel), 2021 Dec 25; 13(24). PMID: 34944889    Free PMC article.
Our current understanding of checkpoint inhibitor therapy in cancer immunotherapy.
Elena Goleva, Taras Lyubchenko, +3 authors, Jeffrey A Kern.
Ann Allergy Asthma Immunol, 2021 Mar 16; 126(6). PMID: 33716146    Free PMC article.
Review.
Development of a fully canine anti-canine CTLA4 monoclonal antibody for comparative translational research in dogs with spontaneous tumors.
Nicola J Mason, Nicholas Chester, +6 authors, Don L Siegel.
MAbs, 2021 Dec 04; 13(1). PMID: 34856888    Free PMC article.
Vectorized Treg-depleting αCTLA-4 elicits antigen cross-presentation and CD8+ T cell immunity to reject 'cold' tumors.
Monika Semmrich, Jean-Baptiste Marchand, +15 authors, Björn Frendéus.
J Immunother Cancer, 2022 Jan 22; 10(1). PMID: 35058324    Free PMC article.
Epitranscriptomics modifier pentostatin indirectly triggers Toll-like receptor 3 and can enhance immune infiltration in tumors.
Marina Tusup, Thomas M Kündig, Steve Pascolo.
Mol Ther, 2021 Sep 27; 30(3). PMID: 34563676    Free PMC article.