Journal Article
. 2018 Mar; 33(4):649-663.e4.
doi: 10.1016/j.ccell.2018.02.010.

Fc Effector Function Contributes to the Activity of Human Anti-CTLA-4 Antibodies

Frederick Arce Vargas 1 Andrew J S Furness 2 Kevin Litchfield 3 Kroopa Joshi 2 Rachel Rosenthal 4 Ehsan Ghorani 1 Isabelle Solomon 1 Marta H Lesko 1 Nora Ruef 1 Claire Roddie 1 Jake Y Henry 1 Lavinia Spain 5 Assma Ben Aissa 1 Andrew Georgiou 1 Yien Ning Sophia Wong 1 Myles Smith 5 Dirk Strauss 5 Andrew Hayes 5 David Nicol 5 Tim O'Brien 6 Linda Mårtensson 7 Anne Ljungars 7 Ingrid Teige 7 Björn Frendéus 7 TRACERx Melanoma  TRACERx Renal  TRACERx Lung consortia  Martin Pule 8 Teresa Marafioti 9 Martin Gore 5 James Larkin 5 Samra Turajlic 10 Charles Swanton 11 Karl S Peggs 12 Sergio A Quezada 13 
  • PMID: 29576375
  •     54 References
  •     199 citations


With the use of a mouse model expressing human Fc-gamma receptors (FcγRs), we demonstrated that antibodies with isotypes equivalent to ipilimumab and tremelimumab mediate intra-tumoral regulatory T (Treg) cell depletion in vivo, increasing the CD8+ to Treg cell ratio and promoting tumor rejection. Antibodies with improved FcγR binding profiles drove superior anti-tumor responses and survival. In patients with advanced melanoma, response to ipilimumab was associated with the CD16a-V158F high affinity polymorphism. Such activity only appeared relevant in the context of inflamed tumors, explaining the modest response rates observed in the clinical setting. Our data suggest that the activity of anti-CTLA-4 in inflamed tumors may be improved through enhancement of FcγR binding, whereas poorly infiltrated tumors will likely require combination approaches.

Keywords: CTLA-4; Fc-gamma receptors; IgG subclass; antibody-dependent cell-mediated cytotoxicity; immune checkpoints; immune regulatory antibodies; ipilimumab; regulatory T cell depletion; tremelimumab; tumor immunotherapy.

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Nat Commun, 2019 May 21; 10(1). PMID: 31105267    Free PMC article.
Phosphoinositide 3-kinase δ is a regulatory T-cell target in cancer immunotherapy.
Ee Lyn Lim, Klaus Okkenhaug.
Immunology, 2019 May 21; 157(3). PMID: 31107985    Free PMC article.
Toward a comprehensive view of cancer immune responsiveness: a synopsis from the SITC workshop.
Davide Bedognetti, Michele Ceccarelli, +53 authors, Society for Immunotherapy of Cancer (SITC) Cancer Immune Responsiveness Task Force and Working Groups.
J Immunother Cancer, 2019 May 23; 7(1). PMID: 31113486    Free PMC article.
Anti-CTLA-4 Immunotherapy Does Not Deplete FOXP3+ Regulatory T Cells (Tregs) in Human Cancers-Response.
Anu Sharma, Sumit K Subudhi, +5 authors, Padmanee Sharma.
Clin Cancer Res, 2019 Jun 05; 25(11). PMID: 31160495    Free PMC article.
Regulatory T cells in cancer: where are we now?
Awen Gallimore, Sergio A Quezada, Rahul Roychoudhuri.
Immunology, 2019 Jun 22; 157(3). PMID: 31225653    Free PMC article.
Functional diversification of hybridoma-produced antibodies by CRISPR/HDR genomic engineering.
Johan M S van der Schoot, Felix L Fennemann, +18 authors, Ferenc A Scheeren.
Sci Adv, 2019 Sep 07; 5(8). PMID: 31489367    Free PMC article.
Regulatory T Cells in Tumor Microenvironment and Approach for Anticancer Immunotherapy.
Jung-Ho Kim, Beom Seok Kim, Sang-Kyou Lee.
Immune Netw, 2020 Mar 12; 20(1). PMID: 32158592    Free PMC article.
Conducting a Virtual Clinical Trial in HER2-Negative Breast Cancer Using a Quantitative Systems Pharmacology Model With an Epigenetic Modulator and Immune Checkpoint Inhibitors.
Hanwen Wang, Richard J Sové, +6 authors, Aleksander S Popel.
Front Bioeng Biotechnol, 2020 Mar 12; 8. PMID: 32158754    Free PMC article.
Multi-Dimensional Flow Cytometry Analyses Reveal a Dichotomous Role for Nitric Oxide in Melanoma Patients Receiving Immunotherapy.
Saurabh K Garg, Matthew J Ott, +12 authors, Joseph Markowitz.
Front Immunol, 2020 Mar 13; 11. PMID: 32161584    Free PMC article.
Mechanism- and Immune Landscape-Based Ranking of Therapeutic Responsiveness of 22 Major Human Cancers to Next Generation Anti-CTLA-4 Antibodies.
Peng Zhang, Xinxin Xiong, +8 authors, Pan Zheng.
Cancers (Basel), 2020 Jan 30; 12(2). PMID: 31991588    Free PMC article.
Immunotherapy of multiple myeloma.
Simone A Minnie, Geoffrey R Hill.
J Clin Invest, 2020 Mar 10; 130(4). PMID: 32149732    Free PMC article.
Depleting tumor-associated Tregs via nanoparticle-mediated hyperthermia to enhance anti-CTLA-4 immunotherapy.
Hongwei Chen, Xin Luan, +7 authors, Duxin Sun.
Nanomedicine (Lond), 2019 Dec 24; 15(1). PMID: 31868112    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.
Impact of Human FcγR Gene Polymorphisms on IgG-Triggered Cytokine Release: Critical Importance of Cell Assay Format.
Khiyam Hussain, Chantal E Hargreaves, +9 authors, Mark S Cragg.
Front Immunol, 2019 Mar 23; 10. PMID: 30899264    Free PMC article.
Targeting the Antibody Checkpoints to Enhance Cancer Immunotherapy-Focus on FcγRIIB.
Ingrid Teige, Linda Mårtensson, Björn L Frendéus.
Front Immunol, 2019 Apr 02; 10. PMID: 30930905    Free PMC article.
Combining Immune Checkpoint Inhibitors: Established and Emerging Targets and Strategies to Improve Outcomes in Melanoma.
Duaa O Khair, Heather J Bax, +22 authors, Sophia N Karagiannis.
Front Immunol, 2019 Apr 04; 10. PMID: 30941125    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.
IgG and Fcγ Receptors in Intestinal Immunity and Inflammation.
Tomas Castro-Dopico, Menna R Clatworthy.
Front Immunol, 2019 Apr 30; 10. PMID: 31031776    Free PMC article.
Immunometabolic Checkpoints of Treg Dynamics: Adaptation to Microenvironmental Opportunities and Challenges.
Ilenia Pacella, Silvia Piconese.
Front Immunol, 2019 Sep 12; 10. PMID: 31507585    Free PMC article.
Clinical Pharmacokinetic and Pharmacodynamic Considerations in the (Modern) Treatment of Melanoma.
Hannah Yejin Kim, Parth J Upadhyay, +3 authors, Alan V Boddy.
Clin Pharmacokinet, 2019 Mar 15; 58(8). PMID: 30868471
Reprogramming the Constant Region of Immunoglobulin G Subclasses for Enhanced Therapeutic Potency against Cancer.
Tae Hyun Kang, Sang Taek Jung.
Biomolecules, 2020 Mar 04; 10(3). PMID: 32121592    Free PMC article.
Preserving the CTLA-4 Checkpoint for Safer and More Effective Cancer Immunotherapy.
Yang Liu, Pan Zheng.
Trends Pharmacol Sci, 2019 Dec 15; 41(1). PMID: 31836191    Free PMC article.
The Fully human anti-CD47 antibody SRF231 exerts dual-mechanism antitumor activity via engagement of the activating receptor CD32a.
Marisa O Peluso, Ammar Adam, +10 authors, Alison M Paterson.
J Immunother Cancer, 2020 Apr 30; 8(1). PMID: 32345627    Free PMC article.
Normalization Cancer Immunotherapy for Melanoma.
Matthew D Vesely, Lieping Chen.
J Invest Dermatol, 2020 Feb 25; 140(6). PMID: 32092349    Free PMC article.
The Tumor Microenvironment in the Response to Immune Checkpoint Blockade Therapies.
Florent Petitprez, Maxime Meylan, +2 authors, Wolf H Fridman.
Front Immunol, 2020 May 28; 11. PMID: 32457745    Free PMC article.
Bcl6 Preserves the Suppressive Function of Regulatory T Cells During Tumorigenesis.
Yiding Li, Zhiming Wang, +16 authors, Lifan Xu.
Front Immunol, 2020 Jun 02; 11. PMID: 32477338    Free PMC article.
A conserved intratumoral regulatory T cell signature identifies 4-1BB as a pan-cancer target.
Zachary T Freeman, Thomas R Nirschl, +17 authors, Charles G Drake.
J Clin Invest, 2020 Feb 06; 130(3). PMID: 32015231    Free PMC article.
PD-1: Its Discovery, Involvement in Cancer Immunotherapy, and Beyond.
Yasumasa Ishida.
Cells, 2020 Jun 05; 9(6). PMID: 32492969    Free PMC article.
Regulatory T cells in tumor microenvironment: new mechanisms, potential therapeutic strategies and future prospects.
Chunxiao Li, Ping Jiang, +2 authors, Junjie Wang.
Mol Cancer, 2020 Jul 19; 19(1). PMID: 32680511    Free PMC article.
Regulatory T Cells Restrain Interleukin-2- and Blimp-1-Dependent Acquisition of Cytotoxic Function by CD4+ T Cells.
Anna Śledzińska, Maria Vila de Mucha, +19 authors, Sergio A Quezada.
Immunity, 2020 Jan 12; 52(1). PMID: 31924474    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.
Glucometabolic Reprogramming in the Hepatocellular Carcinoma Microenvironment: Cause and Effect.
Huining Tian, Xiaoyu Zhu, +2 authors, Guixia Wang.
Cancer Manag Res, 2020 Aug 09; 12. PMID: 32765096    Free PMC article.
Radiation-induced bystander and abscopal effects: important lessons from preclinical models.
Elisabeth Daguenet, Safa Louati, +6 authors, Nicolas Magné.
Br J Cancer, 2020 Jun 26; 123(3). PMID: 32581341    Free PMC article.
Myeloid Cells as Clinical Biomarkers for Immune Checkpoint Blockade.
Elisa Peranzoni, Vincenzo Ingangi, +2 authors, Ilaria Marigo.
Front Immunol, 2020 Aug 15; 11. PMID: 32793228    Free PMC article.
Prognostic value of FoxP3 and CTLA-4 expression in patients with oral squamous cell carcinoma.
Kazushige Koike, Hironari Dehari, +10 authors, Akihiro Miyazaki.
PLoS One, 2020 Aug 14; 15(8). PMID: 32785290    Free PMC article.
Re-education of the Tumor Microenvironment With Targeted Therapies and Immunotherapies.
Shin Foong Ngiow, Arabella Young.
Front Immunol, 2020 Aug 28; 11. PMID: 32849557    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.
Combining BRAF inhibition with oncolytic herpes simplex virus enhances the immune-mediated antitumor therapy of BRAF-mutant thyroid cancer.
Eva Crespo-Rodriguez, Katharina Bergerhoff, +15 authors, Malin Pedersen.
J Immunother Cancer, 2020 Aug 08; 8(2). PMID: 32759235    Free PMC article.
Deep immune profiling of ovarian tumors identifies minimal MHC-I expression after neoadjuvant chemotherapy as negatively associated with T-cell-dependent outcome.
Kim L Brunekreeft, Sterre T Paijens, +13 authors, Marco De Bruyn.
Oncoimmunology, 2020 Sep 15; 9(1). PMID: 32923120    Free PMC article.
Biomarkers of immunotherapy in non-small cell lung cancer.
Lingling Wang, Yue Hu, +2 authors, Xiaochen Wang.
Oncol Lett, 2020 Sep 17; 20(5). PMID: 32934707    Free PMC article.
The clinical promise of immunotherapy in triple-negative breast cancer.
Praveen Vikas, Nicholas Borcherding, Weizhou Zhang.
Cancer Manag Res, 2018 Dec 24; 10. PMID: 30573992    Free PMC article.
Cytokines, Chemokines, and Other Biomarkers of Response for Checkpoint Inhibitor Therapy in Skin Cancer.
Jennifer A Bridge, James C Lee, +2 authors, Jeffrey A Bluestone.
Front Med (Lausanne), 2019 Jan 12; 5. PMID: 30631766    Free PMC article.
Antibody and fragment-based PET imaging of CTLA-4+ T-cells in humanized mouse models.
Emily B Ehlerding, Hye Jin Lee, +6 authors, Weibo Cai.
Am J Cancer Res, 2019 Feb 14; 9(1). PMID: 30755811    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.
Immune Checkpoint Ligand Reverse Signaling: Looking Back to Go Forward in Cancer Therapy.
Daniele Lecis, Sabina Sangaletti, Mario P Colombo, Claudia Chiodoni.
Cancers (Basel), 2019 May 08; 11(5). PMID: 31060225    Free PMC article.
TIGIT in cancer immunotherapy.
Joe-Marc Chauvin, Hassane M Zarour.
J Immunother Cancer, 2020 Sep 10; 8(2). PMID: 32900861    Free PMC article.
Selective inhibition of TGF-β1 produced by GARP-expressing Tregs overcomes resistance to PD-1/PD-L1 blockade in cancer.
Grégoire de Streel, Charlotte Bertrand, +17 authors, Sophie Lucas.
Nat Commun, 2020 Sep 13; 11(1). PMID: 32917858    Free PMC article.
New biomarkers for checkpoint inhibitor therapy.
Nikki Burdett, Jayesh Desai.
ESMO Open, 2020 Sep 17; 5(Suppl 1). PMID: 32933940    Free PMC article.
Hyperprogression: A novel response pattern under immunotherapy.
Xue-Jiao Han, Aqu Alu, +2 authors, Xia-Wei Wei.
Clin Transl Med, 2020 Oct 01; 10(5). PMID: 32997401    Free PMC article.
Development and characterization of CD54-targeted immunoPET imaging in solid tumors.
Weijun Wei, Dawei Jiang, +5 authors, Weibo Cai.
Eur J Nucl Med Mol Imaging, 2020 Apr 13; 47(12). PMID: 32279097    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.
Genomics-based immuno-oncology: bridging the gap between immunology and tumor biology.
Renzo G DiNatale, A Ari Hakimi, Timothy A Chan.
Hum Mol Genet, 2020 Oct 09; 29(R2). PMID: 33029628    Free PMC article.
Immune checkpoint inhibition therapy for advanced skin cancer in patients with concomitant hematological malignancy: a retrospective multicenter DeCOG study of 84 patients.
Ulrike Leiter, Carmen Loquai, +26 authors, Selma Ugurel.
J Immunother Cancer, 2020 Oct 24; 8(2). PMID: 33093156    Free PMC article.
Antitumor efficacy of combined CTLA4/PD-1 blockade without intestinal inflammation is achieved by elimination of FcγR interactions.
David Bauché, Smita Mauze, +11 authors, Drake Laface.
J Immunother Cancer, 2020 Nov 01; 8(2). PMID: 33127658    Free PMC article.
Immune Checkpoints and CAR-T Cells: The Pioneers in Future Cancer Therapies?
Negar Hosseinkhani, Afshin Derakhshani, +9 authors, Behzad Baradaran.
Int J Mol Sci, 2020 Nov 11; 21(21). PMID: 33167514    Free PMC article.
Transcriptional Control of Regulatory T Cells in Cancer: Toward Therapeutic Targeting?
Pierre Stéphan, Raphaëlle Lautraite, Allison Voisin, Yenkel Grinberg-Bleyer.
Cancers (Basel), 2020 Nov 05; 12(11). PMID: 33143070    Free PMC article.
Mechanisms of Resistance to Immune Checkpoint Blockade.
David Liu, Russell W Jenkins, Ryan J Sullivan.
Am J Clin Dermatol, 2018 Sep 28; 20(1). PMID: 30259383    Free PMC article.
A Paradigm Shift in Cancer Immunotherapy: From Enhancement to Normalization.
Miguel F Sanmamed, Lieping Chen.
Cell, 2018 Oct 06; 175(2). PMID: 30290139    Free PMC article.
Highly Cited. Review.
The evolving landscape of biomarkers for checkpoint inhibitor immunotherapy.
Jonathan J Havel, Diego Chowell, Timothy A Chan.
Nat Rev Cancer, 2019 Feb 14; 19(3). PMID: 30755690    Free PMC article.
Highly Cited. Review.
Synergistic effect of immune checkpoint blockade and anti-angiogenesis in cancer treatment.
Ming Yi, Dechao Jiao, +3 authors, Anping Li.
Mol Cancer, 2019 Mar 31; 18(1). PMID: 30925919    Free PMC article.
Highly Cited. Review.
CTLA-4 antibody ipilimumab negatively affects CD4+ T-cell responses in vitro.
Sandra Rosskopf, Judith Leitner, Gerhard J Zlabinger, Peter Steinberger.
Cancer Immunol Immunother, 2019 Jul 25; 68(8). PMID: 31332464    Free PMC article.
Fc-Engineering for Modulated Effector Functions-Improving Antibodies for Cancer Treatment.
Rena Liu, Robert J Oldham, +2 authors, Mark S Cragg.
Antibodies (Basel), 2020 Nov 21; 9(4). PMID: 33212886    Free PMC article.
Overcoming Immune Evasion in Melanoma.
Kevinn Eddy, Suzie Chen.
Int J Mol Sci, 2020 Dec 02; 21(23). PMID: 33256089    Free PMC article.
Targeting the myeloid checkpoint receptor SIRPα potentiates innate and adaptive immune responses to promote anti-tumor activity.
Tracy C Kuo, Amy Chen, +12 authors, Hong I Wan.
J Hematol Oncol, 2020 Dec 02; 13(1). PMID: 33256806    Free PMC article.
Regulation of PD-L1 Expression by NF-κB in Cancer.
Fabrizio Antonangeli, Ambra Natalini, +3 authors, Francesca Di Rosa.
Front Immunol, 2020 Dec 17; 11. PMID: 33324403    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.
Cyclophosphamide Enhances Cancer Antibody Immunotherapy in the Resistant Bone Marrow Niche by Modulating Macrophage FcγR Expression.
Ali Roghanian, Guangan Hu, +12 authors, Jianzhu Chen.
Cancer Immunol Res, 2019 Aug 28; 7(11). PMID: 31451483    Free PMC article.
The Current Landscape of Antibody-based Therapies in Solid Malignancies.
Ashu Shah, Sanchita Rauth, +6 authors, Surinder K Batra.
Theranostics, 2021 Jan 05; 11(3). PMID: 33391547    Free PMC article.
Identification of lncRNA-mRNA Regulatory Module to Explore the Pathogenesis and Prognosis of Melanoma.
Jiaqi Zhang, Hui Liu, +4 authors, Judong Luo.
Front Cell Dev Biol, 2021 Jan 05; 8. PMID: 33392203    Free PMC article.
Domain binding and isotype dictate the activity of anti-human OX40 antibodies.
Jordana Griffiths, Khiyam Hussain, +18 authors, Mark S Cragg.
J Immunother Cancer, 2021 Jan 12; 8(2). PMID: 33428585    Free PMC article.
Immunodynamics of explanted human tumors for immuno-oncology.
Agathe Dubuisson, Jean-Eudes Fahrner, +43 authors, Laurence Zitvogel.
EMBO Mol Med, 2020 Dec 30; 13(1). PMID: 33372722    Free PMC article.
Therapeutic targeting of TGF-β in cancer: hacking a master switch of immune suppression.
Jitske van den Bulk, Noel F C C de Miranda, Peter Ten Dijke.
Clin Sci (Lond), 2021 Jan 06; 135(1). PMID: 33399850    Free PMC article.
Rethinking immune checkpoint blockade: 'Beyond the T cell'.
Xiuting Liu, Graham D Hogg, David G DeNardo.
J Immunother Cancer, 2021 Jan 21; 9(1). PMID: 33468555    Free PMC article.
Intratumoral IL-12 delivery empowers CAR-T cell immunotherapy in a pre-clinical model of glioblastoma.
Giulia Agliardi, Anna Rita Liuzzi, +17 authors, Burkhard Becher.
Nat Commun, 2021 Jan 21; 12(1). PMID: 33469002    Free PMC article.
Understanding and Targeting Human Cancer Regulatory T Cells to Improve Therapy.
H Ryan Kolb, Nicholas Borcherding, Weizhou Zhang.
Adv Exp Med Biol, 2021 Feb 02; 1278. PMID: 33523451
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.
Activity of murine surrogate antibodies for durvalumab and tremelimumab lacking effector function and the ability to deplete regulatory T cells in mouse models of cancer.
Darren J Schofield, Jennifer Percival-Alwyn, +18 authors, Michael Oberst.
MAbs, 2021 Jan 06; 13(1). PMID: 33397194    Free PMC article.
Modulation of regulatory T cell function and stability by co-inhibitory receptors.
Liliana E Lucca, Margarita Dominguez-Villar.
Nat Rev Immunol, 2020 Apr 10; 20(11). PMID: 32269380
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.
Isotype selection for antibody-based cancer therapy.
N Vukovic, A van Elsas, J S Verbeek, D M W Zaiss.
Clin Exp Immunol, 2020 Nov 07; 203(3). PMID: 33155272    Free PMC article.
Ex vivo modelling of PD-1/PD-L1 immune checkpoint blockade under acute, chronic, and exhaustion-like conditions of T-cell stimulation.
Alexander Roberts, Lindsay Bentley, +24 authors, Nicholas M Barnes.
Sci Rep, 2021 Feb 19; 11(1). PMID: 33597595    Free PMC article.
Accelerating target deconvolution for therapeutic antibody candidates using highly parallelized genome editing.
Jenny Mattsson, Ludvig Ekdahl, +7 authors, Björn Nilsson.
Nat Commun, 2021 Feb 26; 12(1). PMID: 33627649    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.
Natural Killer Cells and Anti-Cancer Therapies: Reciprocal Effects on Immune Function and Therapeutic Response.
Elisa C Toffoli, Abdolkarim Sheikhi, +6 authors, Tanja D de Gruijl.
Cancers (Basel), 2021 Feb 13; 13(4). PMID: 33572396    Free PMC article.
CD25-Treg-depleting antibodies preserving IL-2 signaling on effector T cells enhance effector activation and antitumor immunity.
Isabelle Solomon, Maria Amann, +29 authors, Sergio A Quezada.
Nat Cancer, 2021 Mar 02; 1(12). PMID: 33644766    Free PMC article.
Non-canonical PD-1 signaling in cancer and its potential implications in clinic.
Haoran Zha, Ying Jiang, +10 authors, Zhaoxia Li.
J Immunother Cancer, 2021 Feb 18; 9(2). PMID: 33593825    Free PMC article.
Immune Deregulation in Sepsis and Septic Shock: Reversing Immune Paralysis by Targeting PD-1/PD-L1 Pathway.
Yuki Nakamori, Eun Jeong Park, Motomu Shimaoka.
Front Immunol, 2021 Mar 09; 11. PMID: 33679715    Free PMC article.
Advances in Human Immune System Mouse Models for Personalized Treg-Based Immunotherapies.
Isabelle Serr, Maria Kral, Martin G Scherm, Carolin Daniel.
Front Immunol, 2021 Mar 09; 12. PMID: 33679808    Free PMC article.
Augmented antibody-based anticancer therapeutics boost neutrophil cytotoxicity.
Niels Heemskerk, Mandy Gruijs, +14 authors, Marjolein van Egmond.
J Clin Invest, 2021 Feb 10; 131(6). PMID: 33561014    Free PMC article.
Autoimmune complications of cancer immunotherapy.
Kavita M Dhodapkar.
Curr Opin Immunol, 2019 Sep 27; 61. PMID: 31557690    Free PMC article.
Immunotherapy Goes Local: The Central Role of Lymph Nodes in Driving Tumor Infiltration and Efficacy.
Kim M van Pul, Marieke F Fransen, Rieneke van de Ven, Tanja D de Gruijl.
Front Immunol, 2021 Mar 19; 12. PMID: 33732264    Free PMC article.
Generation of FX-/- and Gmds-/- CHOZN host cell lines for the production of afucosylated therapeutic antibodies.
Weiyi Liu, Roshan Padmashali, +8 authors, Bohong Zhang.
Biotechnol Prog, 2020 Aug 05; 37(1). PMID: 32748555    Free PMC article.
Tumor-infiltrating lymphocytes in the immunotherapy era.
Sterre T Paijens, Annegé Vledder, Marco de Bruyn, Hans W Nijman.
Cell Mol Immunol, 2020 Nov 04; 18(4). PMID: 33139907    Free PMC article.
Current status and future perspectives of immunotherapy in bladder cancer treatment.
Zhangsong Wu, Jinjian Liu, Ruixiang Dai, Song Wu.
Sci China Life Sci, 2020 Sep 15; 64(4). PMID: 32926318
Challenging Hurdles of Current Targeting in Glioblastoma: A Focus on Immunotherapeutic Strategies.
Vassilis Genoud, Denis Migliorini.
Int J Mol Sci, 2021 Apr 04; 22(7). PMID: 33800593    Free PMC article.
ImmunoPET Imaging of TIM-3 in Murine Melanoma Models.
Weijun Wei, Dawei Jiang, +4 authors, Weibo Cai.
Adv Ther (Weinh), 2021 Apr 24; 3(7). PMID: 33889713    Free PMC article.
Comprehensive description of the current breast cancer microenvironment advancements via single-cell analysis.
Xueqi Yan, Yinghong Xie, +10 authors, Yongmei Yin.
J Exp Clin Cancer Res, 2021 Apr 29; 40(1). PMID: 33906694    Free PMC article.
Refractory Immune Checkpoint Inhibitor-Induced Colitis Improved by Tacrolimus: A Case Report.
Yasuhito Kunogi, Keiichi Tominaga, +10 authors, Atsushi Irisawa.
Healthcare (Basel), 2021 May 01; 9(4). PMID: 33916353    Free PMC article.
CD80 Expression on Tumor Cells Alters Tumor Microenvironment and Efficacy of Cancer Immunotherapy by CTLA-4 Blockade.
Julie Vackova, Ingrid Polakova, Shweta Dilip Johari, Michal Smahel.
Cancers (Basel), 2021 May 01; 13(8). PMID: 33923750    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.
Biological bases of cancer immunotherapy.
Maryanne M Gonzales Carazas, Joseph A Pinto, Fanny L Casado.
Expert Rev Mol Med, 2021 Mar 26; 23. PMID: 33762030    Free PMC article.
Local Depletion of Immune Checkpoint Ligand CTLA4 Expressing Cells in Tumor Beds Enhances Antitumor Host Immunity.
Ryuhei Okada, Takuya Kato, +4 authors, Hisataka Kobayashi.
Adv Ther (Weinh), 2021 May 18; 4(5). PMID: 33997271    Free PMC article.
Tumor-infiltrating CD8+ T cell antitumor efficacy and exhaustion: molecular insights.
Sandeep Kumar, Sunil Kumar Singh, Basabi Rana, Ajay Rana.
Drug Discov Today, 2021 Jan 16; 26(4). PMID: 33450394    Free PMC article.
Nanotechnology synergized immunoengineering for cancer.
Deepak S Chauhan, Anupam Dhasmana, +6 authors, Murali M Yallapu.
Eur J Pharm Biopharm, 2021 Mar 29; 163. PMID: 33774162    Free PMC article.
Impact of Immunotherapy on CD4 T Cell Phenotypes and Function in Cancer.
Margaux Saillard, Mara Cenerenti, Pedro Romero, Camilla Jandus.
Vaccines (Basel), 2021 Jun 03; 9(5). PMID: 34064410    Free PMC article.
Rate of Freeze Impacts the Survival and Immune Responses Post Cryoablation of Melanoma.
Chakradhar Yakkala, Julien Dagher, +5 authors, Rafael Duran.
Front Immunol, 2021 Jun 22; 12. PMID: 34149738    Free PMC article.
Molecular Dynamics Simulations Reveal Interactions of an IgG1 Antibody With Selected Fc Receptors.
Sebastjan Kralj, Milan Hodošček, +4 authors, Janez Konc.
Front Chem, 2021 Jul 20; 9. PMID: 34277572    Free PMC article.
Fundamental and Essential Knowledge for Pathologists Engaged in the Research and Practice of Immune Checkpoint Inhibitor-Based Cancer Immunotherapy.
Terufumi Kubo, Tomoyo Shinkawa, +5 authors, Toshihiko Torigoe.
Front Oncol, 2021 Jul 23; 11. PMID: 34290982    Free PMC article.
The Next-Generation of Combination Cancer Immunotherapy: Epigenetic Immunomodulators Transmogrify Immune Training to Enhance Immunotherapy.
Reza Bayat Mokhtari, Manpreet Sambi, +7 authors, Myron R Szewczuk.
Cancers (Basel), 2021 Jul 25; 13(14). PMID: 34298809    Free PMC article.
Enhancement of epidermal growth factor receptor antibody tumor immunotherapy by glutaminyl cyclase inhibition to interfere with CD47/signal regulatory protein alpha interactions.
Niklas Baumann, Thies Rösner, +12 authors, Thomas Valerius.
Cancer Sci, 2021 Jun 01; 112(8). PMID: 34058788    Free PMC article.
Bioinformatic Analysis of Prognostic and Immune-Related Genes in Pancreatic Cancer.
Ziang Li, Chang Hu, +3 authors, Xuhong Zhou.
Comput Math Methods Med, 2021 Aug 17; 2021. PMID: 34394706    Free PMC article.
Mechanisms of regulatory T cell infiltration in tumors: implications for innovative immune precision therapies.
Hiroyoshi Nishikawa, Shohei Koyama.
J Immunother Cancer, 2021 Aug 01; 9(7). PMID: 34330764    Free PMC article.
Pancreatic Cancer and Immunotherapy: A Clinical Overview.
Florentine E F Timmer, Bart Geboers, +12 authors, Tanja D de Gruijl.
Cancers (Basel), 2021 Aug 28; 13(16). PMID: 34439292    Free PMC article.
Germline genetic contribution to the immune landscape of cancer.
Rosalyn W Sayaman, Mohamad Saad, +23 authors, Davide Bedognetti.
Immunity, 2021 Feb 11; 54(2). PMID: 33567262    Free PMC article.
Dermatologic infections in cancer patients treated with checkpoint inhibitors.
Mytrang H Do, Dulce M Barrios, +6 authors, Mario E Lacouture.
J Am Acad Dermatol, 2021 Mar 22; 85(6). PMID: 33744355    Free PMC article.
Regulatory T Cells in Autoimmunity and Cancer: A Duplicitous Lifestyle.
Aikaterini Hatzioannou, Athina Boumpas, +4 authors, Panayotis Verginis.
Front Immunol, 2021 Sep 21; 12. PMID: 34539668    Free PMC article.
NSCLC Biomarkers to Predict Response to Immunotherapy with Checkpoint Inhibitors (ICI): From the Cells to In Vivo Images.
Virginia Liberini, Annapaola Mariniello, +7 authors, Désirée Deandreis.
Cancers (Basel), 2021 Sep 29; 13(18). PMID: 34572771    Free PMC article.
Remodeling the Tumor Myeloid Landscape to Enhance Antitumor Antibody Immunotherapies.
Khiyam Hussain, Mark S Cragg, Stephen A Beers.
Cancers (Basel), 2021 Oct 14; 13(19). PMID: 34638388    Free PMC article.
Interaction between intestinal microbiota and tumour immunity in the tumour microenvironment.
Xiuxiu Yang, Yaxin Guo, +7 authors, Zhenqiang Sun.
Immunology, 2021 Jul 30; 164(3). PMID: 34322877    Free PMC article.
Trough levels of ipilimumab in serum as a potential biomarker of clinical outcomes for patients with advanced melanoma after treatment with ipilimumab.
Yoshinobu Koguchi, Noriko Iwamoto, +6 authors, William L Redmond.
J Immunother Cancer, 2021 Oct 09; 9(10). PMID: 34620702    Free PMC article.
Research Progress on the Role of Regulatory T Cell in Tumor Microenvironment in the Treatment of Breast Cancer.
Jianyu Liu, Xueying Wang, +3 authors, Zhigao Li.
Front Oncol, 2021 Dec 07; 11. PMID: 34868991    Free PMC article.
A Novel Assessment Model Based on Molecular Subtypes of Hypoxia-Related LncRNAs for Prognosis of Bladder Cancer.
Xianwu Chen, Yan Zhang, +5 authors, Xiaodong Jin.
Front Cell Dev Biol, 2021 Dec 07; 9. PMID: 34869309    Free PMC article.
Foxp3+ CD4+ regulatory T cells control dendritic cells in inducing antigen-specific immunity to emerging SARS-CoV-2 antigens.
Ryuta Uraki, Masaki Imai, +5 authors, Sayuri Yamazaki.
PLoS Pathog, 2021 Dec 10; 17(12). PMID: 34882757    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.
Phase Ib study on the humanized anti-CCR4 antibody, KW-0761, in advanced solid tumors.
Takuro Saito, Koji Kurose, +11 authors, Hisashi Wada.
Nagoya J Med Sci, 2021 Dec 18; 83(4). PMID: 34916725    Free PMC article.
Expansion of tumor-associated Treg cells upon disruption of a CTLA-4-dependent feedback loop.
Francesco Marangoni, Ademi Zhakyp, +10 authors, Thorsten R Mempel.
Cell, 2021 Jun 23; 184(15). PMID: 34157302    Free PMC article.
The foundations of immune checkpoint blockade and the ipilimumab approval decennial.
Alan J Korman, Sarah C Garrett-Thomson, Nils Lonberg.
Nat Rev Drug Discov, 2021 Dec 24;. PMID: 34937915
Predictive Biomarkers for Outcomes of Immune Checkpoint Inhibitors (ICIs) in Melanoma: A Systematic Review.
Joosje C Baltussen, Marij J P Welters, +7 authors, Nienke A de Glas.
Cancers (Basel), 2021 Dec 25; 13(24). PMID: 34944986    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.
Mechanisms of immune checkpoint inhibitor-mediated liver injury.
Layla Shojaie, Myra Ali, Andrea Iorga, Lily Dara.
Acta Pharm Sin B, 2022 Jan 14; 11(12). PMID: 35024302    Free PMC article.
Role of Fcγ receptors in HER2-targeted breast cancer therapy.
Antonino Musolino, William J Gradishar, +4 authors, Mark D Pegram.
J Immunother Cancer, 2022 Jan 08; 10(1). PMID: 34992090    Free PMC article.
Combination strategies with PD-1/PD-L1 blockade: current advances and future directions.
Ming Yi, Xiaoli Zheng, +3 authors, Kongming Wu.
Mol Cancer, 2022 Jan 23; 21(1). PMID: 35062949    Free PMC article.
T Cell Memory in Infection, Cancer, and Autoimmunity.
Vincenzo Barnaba.
Front Immunol, 2022 Jan 25; 12. PMID: 35069600    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.
Discovering dominant tumor immune archetypes in a pan-cancer census.
Alexis J Combes, Bushra Samad, +35 authors, Matthew F Krummel.
Cell, 2021 Dec 29; 185(1). PMID: 34963056    Free PMC article.
Improved therapeutic index of an acidic pH-selective antibody.
Peter S Lee, Katherine G MacDonald, +15 authors, Arvind Rajpal.
MAbs, 2022 Feb 23; 14(1). PMID: 35192429    Free PMC article.
Immune checkpoint blockade in HIV.
Celine Gubser, Chris Chiu, Sharon R Lewin, Thomas A Rasmussen.
EBioMedicine, 2022 Feb 06; 76. PMID: 35123267    Free PMC article.
A decade of checkpoint blockade immunotherapy in melanoma: understanding the molecular basis for immune sensitivity and resistance.
Alexander C Huang, Roberta Zappasodi.
Nat Immunol, 2022 Mar 05; 23(5). PMID: 35241833    Free PMC article.
An Fc-Competent Anti-Human TIGIT Blocking Antibody Ociperlimab (BGB-A1217) Elicits Strong Immune Responses and Potent Anti-Tumor Efficacy in Pre-Clinical Models.
Xin Chen, Liu Xue, +23 authors, Tong Zhang.
Front Immunol, 2022 Mar 12; 13. PMID: 35273608    Free PMC article.
Identification of the Crucial Role of CCL22 in F. nucleatum-Related Colorectal Tumorigenesis that Correlates With Tumor Microenvironment and Immune Checkpoint Therapy.
Hufei Wang, Kangjia Luo, +12 authors, Rui Huang.
Front Genet, 2022 Mar 18; 13. PMID: 35295948    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.
Checkpoint Inhibitors and Induction of Celiac Disease-like Condition.
Aaron Lerner, Carina Benzvi.
Biomedicines, 2022 Mar 26; 10(3). PMID: 35327411    Free PMC article.
Agonistic CD27 antibody potency is determined by epitope-dependent receptor clustering augmented through Fc-engineering.
Franziska Heckel, Anna H Turaj, +12 authors, Sean H Lim.
Commun Biol, 2022 Mar 16; 5(1). PMID: 35288635    Free PMC article.
Enabling the next steps in cancer immunotherapy: from antibody-based bispecifics to multispecifics, with an evolving role for bioconjugation chemistry.
Fabien Thoreau, Vijay Chudasama.
RSC Chem Biol, 2022 Apr 02; 3(2). PMID: 35360884    Free PMC article.
HIF activation enhances FcγRIIb expression on mononuclear phagocytes impeding tumor targeting antibody immunotherapy.
Khiyam Hussain, Rena Liu, +28 authors, Mark S Cragg.
J Exp Clin Cancer Res, 2022 Apr 09; 41(1). PMID: 35392965    Free PMC article.
Salvage nivolumab and ipilimumab after prior anti-PD-1/PD-L1 therapy in metastatic renal cell carcinoma: A meta-analysis.
Yuanquan Yang, Sherry V Mori, +5 authors, Ming Yin.
Cancer Med, 2022 Feb 10; 11(7). PMID: 35138046    Free PMC article.
Systematic Review.
Immunomodulatory Properties of Immune Checkpoint Inhibitors-More than Boosting T-Cell Responses?
Michael Kuske, Maximilian Haist, +2 authors, Matthias Bros.
Cancers (Basel), 2022 Apr 13; 14(7). PMID: 35406483    Free PMC article.
Challenges to the broad application of allogeneic natural killer cell immunotherapy of cancer.
Philippa R Kennedy, Martin Felices, Jeffrey S Miller.
Stem Cell Res Ther, 2022 Apr 14; 13(1). PMID: 35414042    Free PMC article.
The immune checkpoint B7x expands tumor-infiltrating Tregs and promotes resistance to anti-CTLA-4 therapy.
Peter John, Marc C Pulanco, +4 authors, Xingxing Zang.
Nat Commun, 2022 May 07; 13(1). PMID: 35523809    Free PMC article.
The Leading Role of the Immune Microenvironment in Multiple Myeloma: A New Target with a Great Prognostic and Clinical Value.
Vanessa Desantis, Francesco Domenico Savino, +5 authors, Monica Montagnani.
J Clin Med, 2022 May 15; 11(9). PMID: 35566637    Free PMC article.
In vivo labeling reveals continuous trafficking of TCF-1+ T cells between tumor and lymphoid tissue.
Zhi Li, Zewen K Tuong, +16 authors, David R Withers.
J Exp Med, 2022 Apr 27; 219(6). PMID: 35472220    Free PMC article.
A review of mechanisms of resistance to immune checkpoint inhibitors and potential strategies for therapy.
Yu Fujiwara, Arjun Mittra, Abdul Rafeh Naqash, Naoko Takebe.
Cancer Drug Resist, 2020 Jun 18; 3(3). PMID: 35582437    Free PMC article.