Journal Article
. 2008 Sep; 105(39):14987-92.
doi: 10.1073/pnas.0806075105.

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 1 Ashish Kamat  Derek Ng Tang  Hong Chen  Jingjing Sun  Patricia Troncoso  Christopher Logothetis  Padmanee Sharma  
  • PMID: 18818309
  •     30 References
  •     236 citations


Significant anti-tumor responses have been reported in a small subset of cancer patients treated with the immunotherapeutic agent anti-CTLA-4 antibody. All clinical trials to date, comprising over 3,000 patients, have been conducted in the metastatic disease setting, which allows for correlation of drug administration with clinical outcome but has limited analyses of intermediate biomarkers to indicate whether the drug has impacted human immune responses within the tumor microenvironment. We conducted a pre-surgical clinical trial in six patients with localized bladder cancer, which allowed for correlation of drug administration with biomarkers in both blood and tumor tissues but did not permit correlation with clinical outcome. We found that CD4 T cells from peripheral blood and tumor tissues of all treated patients had markedly increased expression of inducible costimulator (ICOS). These CD4(+)ICOS(hi) T cells produced IFN-gamma (IFNgamma) and could recognize the tumor antigen NY-ESO-1. Increase in CD4(+)ICOS(hi) cells led to an increase in the ratio of effector to regulatory T cells. To our knowledge, these are the first immunologic changes reported in both tumor tissues and peripheral blood as a result of treatment with anti-CTLA-4 antibody, and they may be used to guide dosing and scheduling of this agent to improve clinical responses.

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Alexander Martens, Kilian Wistuba-Hamprecht, +15 authors, Benjamin Weide.
Clin Cancer Res, 2016 May 14; 22(19). PMID: 27169993    Free PMC article.
Highly Cited.
Monitoring immune responses in the tumor microenvironment.
Jennifer A Wargo, Sangeetha M Reddy, Alexandre Reuben, Padmanee Sharma.
Curr Opin Immunol, 2016 May 31; 41. PMID: 27240055    Free PMC article.
Novel immunotherapeutic approaches to the treatment of urothelial carcinoma.
Akhil Muthigi, Arvin K George, Sam J Brancato, Piyush K Agarwal.
Ther Adv Urol, 2016 Jun 02; 8(3). PMID: 27247630    Free PMC article.
Nonmuscle invasive bladder cancer: a primer on immunotherapy.
Mahir Maruf, Sam J Brancato, Piyush K Agarwal.
Cancer Biol Med, 2016 Jul 28; 13(2). PMID: 27458527    Free PMC article.
Immune checkpoints programmed death 1 ligand 1 and cytotoxic T lymphocyte associated molecule 4 in gastric adenocarcinoma.
Hans A Schlößer, Uta Drebber, +20 authors, Michael von Bergwelt-Baildon.
Oncoimmunology, 2016 Jul 29; 5(5). PMID: 27467911    Free PMC article.
Emerging options for the treatment of melanoma - focus on ipilimumab.
Claire Roddie, Karl S Peggs.
Immunotargets Ther, 2014 Jan 01; 3. PMID: 27482517    Free PMC article.
Regulatory T Cells in the Tumor Microenvironment and Cancer Progression: Role and Therapeutic Targeting.
Belal Chaudhary, Eyad Elkord.
Vaccines (Basel), 2016 Aug 12; 4(3). PMID: 27509527    Free PMC article.
Highly Cited. Review.
A Pilot Study of Preoperative Single-Dose Ipilimumab and/or Cryoablation in Women with Early-Stage Breast Cancer with Comprehensive Immune Profiling.
Heather L McArthur, Adi Diab, +27 authors, Larry Norton.
Clin Cancer Res, 2016 Nov 05; 22(23). PMID: 27566765    Free PMC article.
Ipilimumab reshapes T cell memory subsets in melanoma patients with clinical response.
Joana Felix, Jérome Lambert, +13 authors, Hélène Moins-Teisserenc.
Oncoimmunology, 2016 Sep 14; 5(7). PMID: 27622012    Free PMC article.
Loss of IFN-γ Pathway Genes in Tumor Cells as a Mechanism of Resistance to Anti-CTLA-4 Therapy.
Jianjun Gao, Lewis Zhichang Shi, +13 authors, Padmanee Sharma.
Cell, 2016 Sep 27; 167(2). PMID: 27667683    Free PMC article.
Highly Cited.
Clonal expansion of CD8 T cells in the systemic circulation precedes development of ipilimumab-induced toxicities.
Sumit K Subudhi, Ana Aparicio, +14 authors, Padmanee Sharma.
Proc Natl Acad Sci U S A, 2016 Oct 30; 113(42). PMID: 27698113    Free PMC article.
Highly Cited.
Nivolumab monotherapy in recurrent metastatic urothelial carcinoma (CheckMate 032): a multicentre, open-label, two-stage, multi-arm, phase 1/2 trial.
Padmanee Sharma, Margaret K Callahan, +15 authors, Jonathan E Rosenberg.
Lancet Oncol, 2016 Oct 14; 17(11). PMID: 27733243    Free PMC article.
Highly Cited.
Nivolumab for advanced melanoma: pretreatment prognostic factors and early outcome markers during therapy.
Yoshio Nakamura, Shigehisa Kitano, +8 authors, Naoya Yamazaki.
Oncotarget, 2016 Oct 21; 7(47). PMID: 27764805    Free PMC article.
Recent advances in understanding antitumor immunity.
Rodrigo Ramella Munhoz, Michael Andrew Postow.
F1000Res, 2016 Nov 03; 5. PMID: 27803807    Free PMC article.
Is There Still Room for Cancer Vaccines at the Era of Checkpoint Inhibitors.
Soumaya Karaki, Marie Anson, +4 authors, Eric Tartour.
Vaccines (Basel), 2016 Nov 10; 4(4). PMID: 27827885    Free PMC article.
Targeting Immune Regulatory Networks to Counteract Immune Suppression in Cancer.
Chiara Camisaschi, Viviana Vallacchi, +10 authors, Veronica Huber.
Vaccines (Basel), 2016 Nov 10; 4(4). PMID: 27827921    Free PMC article.
Emerging role of immunotherapy in urothelial carcinoma-Immunobiology/biomarkers.
Randy F Sweis, Matthew D Galsky.
Urol Oncol, 2016 Nov 12; 34(12). PMID: 27836246    Free PMC article.
Systemic, perioperative management of muscle-invasive bladder cancer and future horizons.
Samuel A Funt, Jonathan E Rosenberg.
Nat Rev Clin Oncol, 2016 Nov 23; 14(4). PMID: 27874062    Free PMC article.
The role of immune checkpoint inhibition in the treatment of ovarian cancer.
Stéphanie L Gaillard, Angeles A Secord, Bradley Monk.
Gynecol Oncol Res Pract, 2016 Dec 03; 3. PMID: 27904752    Free PMC article.
Regulatory T cells in cancer immunotherapy.
Atsushi Tanaka, Shimon Sakaguchi.
Cell Res, 2016 Dec 21; 27(1). PMID: 27995907    Free PMC article.
Highly Cited. Review.
Clinical implication of tumor-associated and immunological parameters in melanoma patients treated with ipilimumab.
V Damuzzo, S Solito, +6 authors, S Mandruzzato.
Oncoimmunology, 2017 Jan 27; 5(12). PMID: 28123888    Free PMC article.
Intratumoral modulation of the inducible co-stimulator ICOS by recombinant oncolytic virus promotes systemic anti-tumour immunity.
Dmitriy Zamarin, Rikke B Holmgaard, +6 authors, James P Allison.
Nat Commun, 2017 Feb 15; 8. PMID: 28194010    Free PMC article.
Highly Cited.
The Five Immune Forces Impacting DNA-Based Cancer Immunotherapeutic Strategy.
Suneetha Amara, Venkataswarup Tiriveedhi.
Int J Mol Sci, 2017 Mar 18; 18(3). PMID: 28304339    Free PMC article.
VISTA is an inhibitory immune checkpoint that is increased after ipilimumab therapy in patients with prostate cancer.
Jianjun Gao, John F Ward, +16 authors, Padmanee Sharma.
Nat Med, 2017 Mar 28; 23(5). PMID: 28346412    Free PMC article.
Highly Cited.
β-catenin and PI3Kδ inhibition expands precursor Th17 cells with heightened stemness and antitumor activity.
Kinga Majchrzak, Michelle H Nelson, +9 authors, Chrystal M Paulos.
JCI Insight, 2017 Apr 20; 2(8). PMID: 28422756    Free PMC article.
Structural basis for cancer immunotherapy by the first-in-class checkpoint inhibitor ipilimumab.
Udupi A Ramagopal, Weifeng Liu, +10 authors, Steven C Almo.
Proc Natl Acad Sci U S A, 2017 May 10; 114(21). PMID: 28484017    Free PMC article.
Identifying baseline immune-related biomarkers to predict clinical outcome of immunotherapy.
Sacha Gnjatic, Vincenzo Bronte, +13 authors, Lisa H Butterfield.
J Immunother Cancer, 2017 May 19; 5. PMID: 28515944    Free PMC article.
Highly Cited. Review.
Immunotherapy in pancreatic cancer: Unleash its potential through novel combinations.
Songchuan Guo, Merly Contratto, +2 authors, Jennifer Wu.
World J Clin Oncol, 2017 Jun 24; 8(3). PMID: 28638792    Free PMC article.
Cytokine-induced killer cell therapy for modulating regulatory T cells in patients with non-small cell lung cancer.
Baodan Yu, Junli Wang, +8 authors, Jun Xu.
Exp Ther Med, 2017 Jul 05; 14(1). PMID: 28673007    Free PMC article.
Mechanisms of action and rationale for the use of checkpoint inhibitors in cancer.
Clemence Granier, Eleonore De Guillebon, +7 authors, Eric Tartour.
ESMO Open, 2017 Aug 02; 2(2). PMID: 28761757    Free PMC article.
Highly Cited. Review.
Distinct Cellular Mechanisms Underlie Anti-CTLA-4 and Anti-PD-1 Checkpoint Blockade.
Spencer C Wei, Jacob H Levine, +8 authors, James P Allison.
Cell, 2017 Aug 15; 170(6). PMID: 28803728    Free PMC article.
Highly Cited.
Nanomaterials for cancer immunotherapy.
Wantong Song, Sara N Musetti, Leaf Huang.
Biomaterials, 2017 Sep 30; 148. PMID: 28961532    Free PMC article.
CD4 and CD8 T lymphocyte interplay in controlling tumor growth.
Dmitrij Ostroumov, Nora Fekete-Drimusz, +2 authors, Norman Woller.
Cell Mol Life Sci, 2017 Oct 17; 75(4). PMID: 29032503    Free PMC article.
Peripheral and local predictive immune signatures identified in a phase II trial of ipilimumab with carboplatin/paclitaxel in unresectable stage III or stage IV melanoma.
Rahima Jamal, Réjean Lapointe, +13 authors, Wilson H Miller.
J Immunother Cancer, 2017 Nov 22; 5(1). PMID: 29157311    Free PMC article.
Immunotherapy in metastatic urothelial carcinoma: focus on immune checkpoint inhibition.
Arlene Siefker-Radtke, Brendan Curti.
Nat Rev Urol, 2017 Dec 06; 15(2). PMID: 29205200
Molecular Biomarkers of Primary and Acquired Resistance to T-Cell-Mediated Immunotherapy in Cancer: Landscape, Clinical Implications, and Future Directions.
Young Kwang Chae, Michael S Oh, Francis J Giles.
Oncologist, 2017 Dec 16; 23(4). PMID: 29242279    Free PMC article.
Novel immunotherapy approaches for metastatic urothelial and renal cell carcinoma.
Zhiying Shao, Andrew Z Wang, Daniel J George, Tian Zhang.
Asian J Urol, 2016 Oct 01; 3(4). PMID: 29264195    Free PMC article.
Serum exosomes as predictors of clinical response to ipilimumab in metastatic melanoma.
Marco Tucci, Anna Passarelli, +6 authors, Francesco Silvestris.
Oncoimmunology, 2018 Jan 09; 7(2). PMID: 29308314    Free PMC article.
Chimeric Antigen Receptor T Cell Therapy: Challenges to Bench-to-Bedside Efficacy.
Shivani Srivastava, Stanley R Riddell.
J Immunol, 2018 Jan 10; 200(2). PMID: 29311388    Free PMC article.
Highly Cited. Review.
Enhancing CAR T cell persistence through ICOS and 4-1BB costimulation.
Sonia Guedan, Avery D Posey, +14 authors, Carl H June.
JCI Insight, 2018 Jan 13; 3(1). PMID: 29321369    Free PMC article.
Highly Cited.
New therapies in nonmuscle invasive bladder cancer treatment.
Kareem N Rayn, Graham R Hale, Gustavo Pena-La Grave, Piyush K Agarwal.
Indian J Urol, 2018 Jan 19; 34(1). PMID: 29343907    Free PMC article.
Unwrapping the genomic characteristics of urothelial bladder cancer and successes with immune checkpoint blockade therapy.
Wen Cheng, Dian Fu, Feng Xu, Zhengyu Zhang.
Oncogenesis, 2018 Jan 24; 7(1). PMID: 29358573    Free PMC article.
Relationships between lymphocyte counts and treatment-related toxicities and clinical responses in patients with solid tumors treated with PD-1 checkpoint inhibitors.
Adam Diehl, Mark Yarchoan, +2 authors, Stuart A Grossman.
Oncotarget, 2018 Jan 27; 8(69). PMID: 29371985    Free PMC article.
Highly Cited.
Histopathological and immunophenotypic features of ipilimumab-associated colitis compared to ulcerative colitis.
B L Adler, M K Pezhouh, +15 authors, R A Anders.
J Intern Med, 2018 Feb 22; 283(6). PMID: 29464806    Free PMC article.
Importance of immune monitoring approaches and the use of immune checkpoints for the treatment of diffuse intrinsic pontine glioma: From bench to clinic and vice versa (Review).
Jorge Augusto Borin Scutti.
Int J Oncol, 2018 Feb 28; 52(4). PMID: 29484440    Free PMC article.
Immune Monitoring of Cancer Patients Prior to and During CTLA-4 or PD-1/PD-L1 Inhibitor Treatment.
Antje Tunger, Maximilian Kießler, +4 authors, Marc Schmitz.
Biomedicines, 2018 Mar 02; 6(1). PMID: 29494517    Free PMC article.
Checks and Balances in Autoimmune Vasculitis.
Rebeca Hid Cadena, Wayel H Abdulahad, +4 authors, Elisabeth Brouwer.
Front Immunol, 2018 Mar 10; 9. PMID: 29520282    Free PMC article.
NY-ESO-1 Based Immunotherapy of Cancer: Current Perspectives.
Remy Thomas, Ghaneya Al-Khadairi, +4 authors, Julie Decock.
Front Immunol, 2018 May 18; 9. PMID: 29770138    Free PMC article.
Highly Cited. Review.
Interferon-Gamma at the Crossroads of Tumor Immune Surveillance or Evasion.
Flávia Castro, Ana Patrícia Cardoso, +2 authors, Maria José Oliveira.
Front Immunol, 2018 May 22; 9. PMID: 29780381    Free PMC article.
Highly Cited. Review.
Tune Up In Situ Autovaccination against Solid Tumors with Oncolytic Viruses.
Teresa Nguyen, Naze G Avci, +2 authors, Hong Jiang.
Cancers (Basel), 2018 Jun 03; 10(6). PMID: 29857493    Free PMC article.
Indoleamine 2,3-dioxygenase provides adaptive resistance to immune checkpoint inhibitors in hepatocellular carcinoma.
Zachary J Brown, Su Jong Yu, +7 authors, Tim F Greten.
Cancer Immunol Immunother, 2018 Jul 01; 67(8). PMID: 29959458    Free PMC article.
PD-L1, TIM-3, and CTLA-4 Blockade Fails To Promote Resistance to Secondary Infection with Virulent Strains of Toxoplasma gondii.
Samantha D Splitt, Scott P Souza, +4 authors, Kirk D C Jensen.
Infect Immun, 2018 Jul 04; 86(9). PMID: 29967089    Free PMC article.
Tumor matrix remodeling and novel immunotherapies: the promise of matrix-derived immune biomarkers.
Muhammad Umair Mushtaq, Athanasios Papadas, +4 authors, Fotis Asimakopoulos.
J Immunother Cancer, 2018 Jul 05; 6(1). PMID: 29970158    Free PMC article.
Long term impact of CTLA4 blockade immunotherapy on regulatory and effector immune responses in patients with melanoma.
Janet Retseck, Alexis Nasr, +4 authors, Ahmad A Tarhini.
J Transl Med, 2018 Jul 06; 16(1). PMID: 29973204    Free PMC article.
Immune Profiling of Cancer Patients Treated with Immunotherapy: Advances and Challenges.
Lorenzo Pilla, Cristina Maccalli.
Biomedicines, 2018 Jul 14; 6(3). PMID: 30004433    Free PMC article.
Role of Regulatory T Cells in Tumor-Bearing Mice Treated with Allo-Hematopoietic Stem Cell Transplantation Plus Thymus Transplantation.
Naoki Hosaka.
J Immunol Res, 2018 Jul 31; 2018. PMID: 30057919    Free PMC article.
Treg Fragility: A Prerequisite for Effective Antitumor Immunity?
Abigail E Overacre-Delgoffe, Dario A A Vignali.
Cancer Immunol Res, 2018 Aug 03; 6(8). PMID: 30068755    Free PMC article.
Complete Clinical Remission of Stage IV Triple-Negative Breast Cancer Lung Metastasis Administering Low-Dose Immune Checkpoint Blockade in Combination With Hyperthermia and Interleukin-2.
Ralf Kleef, Ralph Moss, +3 authors, Tibor Bakacs.
Integr Cancer Ther, 2018 Sep 09; 17(4). PMID: 30193538    Free PMC article.
Urine-derived lymphocytes as a non-invasive measure of the bladder tumor immune microenvironment.
Yien Ning Sophia Wong, Kroopa Joshi, +22 authors, Sergio A Quezada.
J Exp Med, 2018 Sep 28; 215(11). PMID: 30257862    Free PMC article.
Prognostic Factors for Checkpoint Inhibitor Based Immunotherapy: An Update With New Evidences.
Xinyu Yan, Shouyue Zhang, +3 authors, Heng Xu.
Front Pharmacol, 2018 Oct 09; 9. PMID: 30294272    Free PMC article.
Identification and validation of a tumor-infiltrating Treg transcriptional signature conserved across species and tumor types.
Angela M Magnuson, Evgeny Kiner, +8 authors, Christophe Benoist.
Proc Natl Acad Sci U S A, 2018 Oct 24; 115(45). PMID: 30348759    Free PMC article.
PD-L1 expression with immune-infiltrate evaluation and outcome prediction in melanoma patients treated with ipilimumab.
Gabriele Madonna, Carmen Ballesteros-Merino, +10 authors, Paolo A Ascierto.
Oncoimmunology, 2018 Dec 14; 7(12). PMID: 30524879    Free PMC article.
Autophagosome-based strategy to monitor apparent tumor-specific CD8 T cells in patients with prostate cancer.
Rieneke van de Ven, Traci L Hilton, +8 authors, Bernard A Fox.
Oncoimmunology, 2018 Dec 14; 7(12). PMID: 30524883    Free PMC article.
Novel Biomarkers for Personalized Cancer Immunotherapy.
Yoshitaro Shindo, Shoichi Hazama, +2 authors, Hiroaki Nagano.
Cancers (Basel), 2019 Aug 25; 11(9). PMID: 31443339    Free PMC article.
Combination anti-CTLA-4 plus anti-PD-1 checkpoint blockade utilizes cellular mechanisms partially distinct from monotherapies.
Spencer C Wei, Nana-Ama A S Anang, +8 authors, James P Allison.
Proc Natl Acad Sci U S A, 2019 Oct 23; 116(45). PMID: 31636208    Free PMC article.
Safety and Efficacy of Therapeutic Cancer Vaccines Alone or in Combination With Immune Checkpoint Inhibitors in Cancer Treatment.
Jing Zhao, Ye Chen, Zhen-Yu Ding, Ji-Yan Liu.
Front Pharmacol, 2019 Nov 05; 10. PMID: 31680963    Free PMC article.
Peripheral immune-based biomarkers in cancer immunotherapy: can we realize their predictive potential?
Andrew B Nixon, Kurt A Schalper, +3 authors, Catherine Fleener.
J Immunother Cancer, 2019 Nov 30; 7(1). PMID: 31775882    Free PMC article.
Anti-PD-1 antibody decreases tumour-infiltrating regulatory T cells.
Kazushige Yoshida, Masanori Okamoto, +13 authors, Naoto Saito.
BMC Cancer, 2020 Jan 10; 20(1). PMID: 31914969    Free PMC article.
Immunosuppressive Tumor Microenvironment Status and Histological Grading of Endometrial Carcinoma.
Julie Antomarchi, Damien Ambrosetti, +6 authors, Heidy Schmid-Antomarchi.
Cancer Microenviron, 2019 May 28; 12(2-3). PMID: 31134527    Free PMC article.
Type 1 diabetes pathogenesis and the role of inhibitory receptors in islet tolerance.
Tijana Martinov, Brian T Fife.
Ann N Y Acad Sci, 2019 Apr 27; 1461(1). PMID: 31025378    Free PMC article.
Bempegaldesleukin selectively depletes intratumoral Tregs and potentiates T cell-mediated cancer therapy.
Meenu Sharma, Hiep Khong, +28 authors, Willem W Overwijk.
Nat Commun, 2020 Feb 02; 11(1). PMID: 32005826    Free PMC article.
Mitochondrial transfer from MSCs to T cells induces Treg differentiation and restricts inflammatory response.
Angela C Court, Alice Le-Gatt, +11 authors, Maroun Khoury.
EMBO Rep, 2020 Jan 28; 21(2). PMID: 31984629    Free PMC article.
CTLA-4: a moving target in immunotherapy.
Behzad Rowshanravan, Neil Halliday, David M Sansom.
Blood, 2017 Nov 10; 131(1). PMID: 29118008    Free PMC article.
Highly Cited. Review.
IFNγ: signalling, epigenetics and roles in immunity, metabolism, disease and cancer immunotherapy.
Lionel B Ivashkiv.
Nat Rev Immunol, 2018 Jun 21; 18(9). PMID: 29921905    Free PMC article.
Highly Cited. Review.
Anti-CTLA-4 Immunotherapy Does Not Deplete FOXP3+ Regulatory T Cells (Tregs) in Human Cancers.
Anu Sharma, Sumit K Subudhi, +6 authors, Padmanee Sharma.
Clin Cancer Res, 2018 Jul 29; 25(4). PMID: 30054281    Free PMC article.
Highly Cited.
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.
CD4+ T cells induce rejection of urothelial tumors after immune checkpoint blockade.
Yuji Sato, Jennifer K Bolzenius, +4 authors, Vivek K Arora.
JCI Insight, 2018 Dec 07; 3(23). PMID: 30518683    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.
Immune checkpoint inhibitors: recent progress and potential biomarkers.
Pramod Darvin, Salman M Toor, Varun Sasidharan Nair, Eyad Elkord.
Exp Mol Med, 2018 Dec 14; 50(12). PMID: 30546008    Free PMC article.
Highly Cited. Review.
Meeting report: Metastasis Research Society (MRS) 17th Biennial conference and associated Young Investigator Satellite Meeting (YISM) on cancer metastasis.
Thomas Beadnell, Lucia Borriello, +9 authors, Thomas R Cox.
Clin Exp Metastasis, 2019 Jan 24; 36(2). PMID: 30673912
Lymphopenia in Cancer Patients and its Effects on Response to Immunotherapy: an opportunity for combination with Cytokines?
Christine Ménétrier-Caux, Isabelle Ray-Coquard, Jean-Yves Blay, Christophe Caux.
J Immunother Cancer, 2019 Mar 30; 7(1). PMID: 30922400    Free PMC article.
Highly Cited. Review.
Negative Co-stimulation Constrains T Cell Differentiation by Imposing Boundaries on Possible Cell States.
Spencer C Wei, Roshan Sharma, +8 authors, James P Allison.
Immunity, 2019 Mar 31; 50(4). PMID: 30926234    Free PMC article.
IFN-γ is a therapeutic target in paraneoplastic cerebellar degeneration.
Lidia Yshii, Béatrice Pignolet, +5 authors, Roland Liblau.
JCI Insight, 2019 Apr 05; 4(7). PMID: 30944244    Free PMC article.
The CTLA-4 x OX40 bispecific antibody ATOR-1015 induces anti-tumor effects through tumor-directed immune activation.
Anne Månsson Kvarnhammar, Niina Veitonmäki, +16 authors, Peter Ellmark.
J Immunother Cancer, 2019 Apr 13; 7(1). PMID: 30975201    Free PMC article.
Inhibition of immune checkpoints PD-1, CTLA-4, and IDO1 coordinately induces immune-mediated liver injury in mice.
Timothy Affolter, Heather P Llewellyn, +4 authors, Changhua Ji.
PLoS One, 2019 May 22; 14(5). PMID: 31112568    Free PMC article.
Immune checkpoint blockade and CAR-T cell therapy in hematologic malignancies.
Hao Wang, Gurbakhash Kaur, +3 authors, Xingxing Zang.
J Hematol Oncol, 2019 Jun 13; 12(1). PMID: 31186046    Free PMC article.
CTLA-4 blockade boosts the expansion of tumor-reactive CD8+ tumor-infiltrating lymphocytes in ovarian cancer.
Christina Friese, Katja Harbst, +7 authors, Özcan Met.
Sci Rep, 2020 Mar 05; 10(1). PMID: 32127601    Free PMC article.
Characteristics of Tumor-Infiltrating Lymphocytes Prior to and During Immune Checkpoint Inhibitor Therapy.
Ioana Plesca, Antje Tunger, +6 authors, Marc Schmitz.
Front Immunol, 2020 Mar 21; 11. PMID: 32194568    Free PMC article.
Combination immunotherapy with anti-PD-L1 antibody and depletion of regulatory T cells during acute viral infections results in improved virus control but lethal immunopathology.
Paul David, Malgorzata Drabczyk-Pluta, +24 authors, Gennadiy Zelinskyy.
PLoS Pathog, 2020 Apr 01; 16(3). PMID: 32226027    Free PMC article.
Development of immune checkpoint therapy for cancer.
Jill M Fritz, Michael J Lenardo.
J Exp Med, 2019 May 10; 216(6). PMID: 31068379    Free PMC article.
Highly Cited. Review.
FcγR-Binding Is an Important Functional Attribute for Immune Checkpoint Antibodies in Cancer Immunotherapy.
Xin Chen, Xiaomin Song, Kang Li, Tong Zhang.
Front Immunol, 2019 Mar 14; 10. PMID: 30863404    Free PMC article.
Highly Cited. Review.
Dawn of Monitoring Regulatory T Cells in (Pre-)clinical Studies: Their Relevance Is Slowly Recognised.
A Charlotte M T de Wolf, Carla A Herberts, Marcel H N Hoefnagel.
Front Med (Lausanne), 2020 Apr 18; 7. PMID: 32300597    Free PMC article.
Systematic Review.
T cell costimulation, checkpoint inhibitors and anti-tumor therapy.
Dipankar Nandi, Sanmoy Pathak, +6 authors, Vijayamahantesh.
J Biosci, 2020 Apr 30; 45. PMID: 32345776
The rationale behind targeting the ICOS-ICOS ligand costimulatory pathway in cancer immunotherapy.
Cinzia Solinas, Chunyan Gu-Trantien, Karen Willard-Gallo.
ESMO Open, 2020 Jun 10; 5(1). PMID: 32516116    Free PMC article.
Intratumoral CD4+ T Cells Mediate Anti-tumor Cytotoxicity in Human Bladder Cancer.
David Y Oh, Serena S Kwek, +17 authors, Lawrence Fong.
Cell, 2020 Jun 05; 181(7). PMID: 32497499    Free PMC article.
Immunological Targets for Immunotherapy: Inhibitory T Cell Receptors.
Diwakar Davar, Hassane M Zarour.
Methods Mol Biol, 2019 Sep 11; 2055. PMID: 31502146    Free PMC article.
Checkpoint inhibitor-related renal vasculitis and use of rituximab.
Omar Mamlouk, Jamie S Lin, +6 authors, Ala Abudayyeh.
J Immunother Cancer, 2020 Jul 29; 8(2). PMID: 32718987    Free PMC article.
Harnessing the Complete Repertoire of Conventional Dendritic Cell Functions for Cancer Immunotherapy.
Lukas Amon, Lukas Hatscher, +2 authors, Christian H K Lehmann.
Pharmaceutics, 2020 Jul 18; 12(7). PMID: 32674488    Free PMC article.
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.
Dose escalation phase 1 study of radiotherapy in combination with anti-cytotoxic-T-lymphocyte-associated antigen 4 monoclonal antibody ipilimumab in patients with metastatic melanoma.
Celine Boutros, Nathalie Chaput-Gras, +17 authors, Eric Deutsch.
J Immunother Cancer, 2020 Aug 21; 8(2). PMID: 32819972    Free PMC article.
Predictive biomarkers for cancer immunotherapy with immune checkpoint inhibitors.
Rilan Bai, Zheng Lv, Dongsheng Xu, Jiuwei Cui.
Biomark Res, 2020 Aug 31; 8. PMID: 32864131    Free PMC article.
Human regulatory T cells (Treg) and their response to cancer.
Theresa L Whiteside.
Expert Rev Precis Med Drug Dev, 2019 Jan 01; 4(4). PMID: 32953989    Free PMC article.
Turning the Tide Against Regulatory T Cells.
SeongJun Han, Aras Toker, Zhe Qi Liu, Pamela S Ohashi.
Front Oncol, 2019 May 07; 9. PMID: 31058083    Free PMC article.
Immunogenicity of Tumor Initiating Stem Cells: Potential Applications in Novel Anticancer Therapy.
Durga Khandekar, Suneetha Amara, Venkataswarup Tiriveedhi.
Front Oncol, 2019 May 21; 9. PMID: 31106150    Free PMC article.
Biomarkers for Immune Checkpoint Inhibitor-Mediated Tumor Response and Adverse Events.
Yoshiyuki Nakamura.
Front Med (Lausanne), 2019 Jun 14; 6. PMID: 31192215    Free PMC article.
Targeting Immune-Mediated Dormancy: A Promising Treatment of Cancer.
Hao-Fan Wang, Sha-Sha Wang, +3 authors, Ya-Ling Tang.
Front Oncol, 2019 Jul 13; 9. PMID: 31297335    Free PMC article.
ICOS+ Tregs: A Functional Subset of Tregs in Immune Diseases.
Dan-Yang Li, Xian-Zhi Xiong.
Front Immunol, 2020 Sep 29; 11. PMID: 32983168    Free PMC article.
Colorectal Cancer Immunotherapy: Options and Strategies.
Nor Adzimah Johdi, Nur Fazilah Sukor.
Front Immunol, 2020 Oct 13; 11. PMID: 33042104    Free PMC article.
Uncoupling Therapeutic Efficacy from Immune-Related Adverse Events in Immune Checkpoint Blockade.
Weilei Hu, Guosheng Wang, +2 authors, Ming You.
iScience, 2020 Oct 22; 23(10). PMID: 33083746    Free PMC article.
Regulatory T Cells in Cancer Immunotherapy: Basic Research Outcomes and Clinical Directions.
Guoming Zeng, Libo Jin, +9 authors, Da Sun.
Cancer Manag Res, 2020 Oct 30; 12. PMID: 33116895    Free PMC article.
Immune Activation in Patients with Locally Advanced Cervical Cancer Treated with Ipilimumab Following Definitive Chemoradiation (GOG-9929).
Diane M Da Silva, Danielle M Enserro, +10 authors, W Martin Kast.
Clin Cancer Res, 2020 Aug 21; 26(21). PMID: 32816895    Free PMC article.
Study and analysis of antitumor resistance mechanism of PD1/PD-L1 immune checkpoint blocker.
Zhengyi Wang, Xiaoying Wu.
Cancer Med, 2020 Sep 03; 9(21). PMID: 32875727    Free PMC article.
A combination trial of vaccine plus ipilimumab in metastatic castration-resistant prostate cancer patients: immune correlates.
Caroline Jochems, Jo A Tucker, +6 authors, Jeffrey Schlom.
Cancer Immunol Immunother, 2014 Feb 12; 63(4). PMID: 24514956    Free PMC article.
Monitoring checkpoint inhibitors: predictive biomarkers in immunotherapy.
Min Zhang, Jingwen Yang, +3 authors, Qijun Qian.
Front Med, 2019 Jan 27; 13(1). PMID: 30680606
Overcoming Immune Evasion in Melanoma.
Kevinn Eddy, Suzie Chen.
Int J Mol Sci, 2020 Dec 02; 21(23). PMID: 33256089    Free PMC article.
Development and Preliminary Clinical Activity of PD-1-Guided CTLA-4 Blocking Bispecific DART Molecule.
Alexey Berezhnoy, Bradley J Sumrow, +16 authors, Paul A Moore.
Cell Rep Med, 2020 Dec 31; 1(9). PMID: 33377134    Free PMC article.
Organized immune cell interactions within tumors sustain a productive T-cell response.
Maria A Cardenas, Nataliya Prokhnevska, Haydn T Kissick.
Int Immunol, 2020 Aug 23; 33(1). PMID: 32827212    Free PMC article.
The Therapeutic Potential of Regulatory T Cells: Challenges and Opportunities.
Fatemeh Bayati, Mahsa Mohammadi, +3 authors, Ehsan Sharif-Paghaleh.
Front Immunol, 2021 Feb 02; 11. PMID: 33519807    Free PMC article.
Neoadjuvant PD-L1 plus CTLA-4 blockade in patients with cisplatin-ineligible operable high-risk urothelial carcinoma.
Jianjun Gao, Neema Navai, +28 authors, Padmanee Sharma.
Nat Med, 2020 Oct 14; 26(12). PMID: 33046869
The science and medicine of human immunology.
Bali Pulendran, Mark M Davis.
Science, 2020 Sep 26; 369(6511). PMID: 32973003    Free PMC article.
Neoadjuvant anti-OX40 (MEDI6469) therapy in patients with head and neck squamous cell carcinoma activates and expands antigen-specific tumor-infiltrating T cells.
Rebekka Duhen, Carmen Ballesteros-Merino, +12 authors, Andrew D Weinberg.
Nat Commun, 2021 Feb 18; 12(1). PMID: 33594075    Free PMC article.
Emerging dynamics pathways of response and resistance to PD-1 and CTLA-4 blockade: tackling uncertainty by confronting complexity.
Allan Relecom, Maysaloun Merhi, +4 authors, Said Dermime.
J Exp Clin Cancer Res, 2021 Feb 20; 40(1). PMID: 33602280    Free PMC article.
CD4+ T Cells: Multitasking Cells in the Duty of Cancer Immunotherapy.
Jennifer R Richardson, Anna Schöllhorn, Cécile Gouttefangeas, Juliane Schuhmacher.
Cancers (Basel), 2021 Feb 07; 13(4). PMID: 33546283    Free PMC article.
PD-L1 and B7-1 Cis-Interaction: New Mechanisms in Immune Checkpoints and Immunotherapies.
Christopher D Nishimura, Marc C Pulanco, +2 authors, Xingxing Zang.
Trends Mol Med, 2020 Nov 18; 27(3). PMID: 33199209    Free PMC article.
T-cell CX3CR1 expression as a dynamic blood-based biomarker of response to immune checkpoint inhibitors.
Takayoshi Yamauchi, Toshifumi Hoki, +13 authors, Fumito Ito.
Nat Commun, 2021 Mar 05; 12(1). PMID: 33658501    Free PMC article.
Therapeutic depletion of CCR8+ tumor-infiltrating regulatory T cells elicits antitumor immunity and synergizes with anti-PD-1 therapy.
Helena Van Damme, Bruno Dombrecht, +26 authors, Jo Agnes Van Ginderachter.
J Immunother Cancer, 2021 Feb 17; 9(2). PMID: 33589525    Free PMC article.
Oncolytic vaccinia virus induces a novel phenotype of CD8+ effector T cells characterized by high ICOS expression.
Midori Yamashita, Mamoru Tasaki, +3 authors, Shinsuke Nakao.
Mol Ther Oncolytics, 2021 Mar 06; 20. PMID: 33665362    Free PMC article.
Use of immune checkpoint inhibitors in cancer patients with pre-existing sarcoidosis.
Sang T Kim, Xerxes Pundole, +3 authors, Maria E Suarez-Almazor.
Immunotherapy, 2021 Mar 02; 13(6). PMID: 33641345    Free PMC article.
The Multifaceted Role of Th1, Th9, and Th17 Cells in Immune Checkpoint Inhibition Therapy.
Jongdae Lee, Beatriz Lozano-Ruiz, +3 authors, Jose M González-Navajas.
Front Immunol, 2021 Mar 30; 12. PMID: 33777008    Free PMC article.
Immunotherapy and predictive immunologic profile: the tip of the iceberg.
Tatiana Cunha Pereira, Paulo Rodrigues-Santos, +7 authors, Gabriela Sousa.
Med Oncol, 2021 Apr 01; 38(5). PMID: 33788049
Non-small cell lung cancer with MET exon 14 skipping alteration responding to immunotherapy: a case report.
Zhuxing Chen, Feng Zhu, +6 authors, Jianxing He.
Ann Transl Med, 2021 Apr 13; 9(5). PMID: 33842645    Free PMC article.
Pre-existing effector T-cell levels and augmented myeloid cell composition denote response to CDK4/6 inhibitor palbociclib and pembrolizumab in hormone receptor-positive metastatic breast cancer.
Colt Egelston, Weihua Guo, +9 authors, Yuan Yuan.
J Immunother Cancer, 2021 Mar 25; 9(3). PMID: 33757987    Free PMC article.
Recruitment and Expansion of Tregs Cells in the Tumor Environment-How to Target Them?
Justine Cinier, Margaux Hubert, +5 authors, Christine Ménétrier-Caux.
Cancers (Basel), 2021 May 01; 13(8). PMID: 33924428    Free PMC article.
Malignant Pleural Effusions-A Window Into Local Anti-Tumor T Cell Immunity?
Nicola Principe, Joel Kidman, +4 authors, Jonathan Chee.
Front Oncol, 2021 May 15; 11. PMID: 33987104    Free PMC article.
Changes in expression of PD-L1 on peripheral T cells in patients with melanoma and lung cancer treated with PD-1 inhibitors.
Sarah J Dart, Alistair M Cook, +5 authors, Samantha E Bowyer.
Sci Rep, 2021 Jul 30; 11(1). PMID: 34321489    Free PMC article.
Inorganic Nanomaterial-Mediated Gene Therapy in Combination with Other Antitumor Treatment Modalities.
Guanyou Lin, Richard A Revia, Miqin Zhang.
Adv Funct Mater, 2021 Aug 10; 31(5). PMID: 34366761    Free PMC article.
The Role of Cytokines in Predicting the Response and Adverse Events Related to Immune Checkpoint Inhibitors.
Min Wang, Xiaoyang Zhai, +4 authors, Hui Zhu.
Front Immunol, 2021 Aug 10; 12. PMID: 34367136    Free PMC article.
Immune Checkpoint Inhibitors Mediated Lymphocytic and Giant Cell Myocarditis: Uncovering Etiological Mechanisms.
Rishi Rikhi, Jaret Karnuta, +5 authors, Rohit Moudgil.
Front Cardiovasc Med, 2021 Aug 27; 8. PMID: 34434981    Free PMC article.
Strategies to Improve the Antitumor Effect of γδ T Cell Immunotherapy for Clinical Application.
Masatsugu Miyashita, Teruki Shimizu, Eishi Ashihara, Osamu Ukimura.
Int J Mol Sci, 2021 Aug 28; 22(16). PMID: 34445615    Free PMC article.
Advancing to the era of cancer immunotherapy.
Yun Wang, Min Wang, Hao-Xiang Wu, Rui-Hua Xu.
Cancer Commun (Lond), 2021 Jun 25; 41(9). PMID: 34165252    Free PMC article.
Role of immunotherapy in localized muscle invasive urothelial cancer.
Jasmeet Kaur, Woonyoung Choi, +2 authors, Pooja Ghatalia.
Ther Adv Med Oncol, 2021 Sep 28; 13. PMID: 34567274    Free PMC article.
Immune landscape in vulvar cancer-draining lymph nodes indicates distinct immune escape mechanisms in support of metastatic spread and growth.
Anne Marijne Heeren, Jossie Rotman, +7 authors, Tanja D de Gruijl.
J Immunother Cancer, 2021 Oct 27; 9(10). PMID: 34697217    Free PMC article.
Comprehensive Analysis to Identify the Epithelial-Mesenchymal Transition-Related Immune Signatures as a Prognostic and Therapeutic Biomarkers in Hepatocellular Carcinoma.
Guozhi Wu, Yuan Yang, +8 authors, Qinghong Guo.
Front Surg, 2021 Nov 02; 8. PMID: 34722623    Free PMC article.
Pilot study of Tremelimumab with and without cryoablation in patients with metastatic renal cell carcinoma.
Matthew T Campbell, Surena F Matin, +19 authors, Padmanee Sharma.
Nat Commun, 2021 Nov 06; 12(1). PMID: 34737281    Free PMC article.
IFNγ induces JAK1/STAT1/p65 NFκB-dependent interleukin-8 expression in ovarian cancer cells, resulting in their increased migration.
Sveta Padmanabhan, Bijaya Gaire, +3 authors, Ivana Vancurova.
Int J Biochem Cell Biol, 2021 Oct 10; 141. PMID: 34626802    Free PMC article.
T cell receptor (TCR) signaling in health and disease.
Kinjal Shah, Amr Al-Haidari, Jianmin Sun, Julhash U Kazi.
Signal Transduct Target Ther, 2021 Dec 14; 6(1). PMID: 34897277    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.
Hallmarks of response, resistance, and toxicity to immune checkpoint blockade.
Golnaz Morad, Beth A Helmink, Padmanee Sharma, Jennifer A Wargo.
Cell, 2021 Oct 09; 184(21). PMID: 34624224    Free PMC article.
IFN-Gamma Expression in the Tumor Microenvironment and CD8-Positive Tumor-Infiltrating Lymphocytes as Prognostic Markers in Urothelial Cancer Patients Receiving Pembrolizumab.
Toru Sakatani, Yuki Kita, +8 authors, Takashi Kobayashi.
Cancers (Basel), 2022 Jan 22; 14(2). PMID: 35053427    Free PMC article.
Connecting blood and intratumoral Treg cell activity in predicting future relapse in breast cancer.
Lei Wang, Diana L Simons, +9 authors, Peter P Lee.
Nat Immunol, 2019 Jul 10; 20(9). PMID: 31285626    Free PMC article.
Highly Cited.
Cytotoxic CD4+ T cells in cancer: Expanding the immune effector toolbox.
David Y Oh, Lawrence Fong.
Immunity, 2021 Dec 16; 54(12). PMID: 34910940    Free PMC article.
Addressing the Elephant in the Immunotherapy Room: Effector T-Cell Priming versus Depletion of Regulatory T-Cells by Anti-CTLA-4 Therapy.
Megan M Y Hong, Saman Maleki Vareki.
Cancers (Basel), 2022 Mar 26; 14(6). PMID: 35326731    Free PMC article.
Brain radiotherapy, tremelimumab-mediated CTLA-4-directed blockade +/- trastuzumab in patients with breast cancer brain metastases.
David B Page, Kathryn Beal, +14 authors, Heather L McArthur.
NPJ Breast Cancer, 2022 Apr 21; 8(1). PMID: 35440655    Free PMC article.
Exploring the Mechanisms Underlying the Cardiotoxic Effects of Immune Checkpoint Inhibitor Therapies.
Daniel Ronen, Aseel Bsoul, +4 authors, Rabea Asleh.
Vaccines (Basel), 2022 Apr 24; 10(4). PMID: 35455289    Free PMC article.
Single-Cell RNA-Seq and Bulk RNA-Seq Reveal Intratumoral Heterogeneity and Tumor Microenvironment Characteristics in Diffuse Large B-Cell Lymphoma.
Yang Zhao, Hui Xu, Mingzhi Zhang, Ling Li.
Front Genet, 2022 May 24; 13. PMID: 35601491    Free PMC article.
Neoadjuvant immunotherapy across cancers: meeting report from the Immunotherapy Bridge-December 1st-2nd, 2021.
Elizabeth M Burton, Rodabe N Amaria, +6 authors, Paolo A Ascierto.
J Transl Med, 2022 Jun 16; 20(1). PMID: 35706041