. 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  
  • PMID: 23390376
  •     102 References
  •     156 citations


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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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.
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.
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.
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
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.
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.
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.
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
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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
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.
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.
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.
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.
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
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.
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.
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
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.
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
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.