Immune checkpoint therapy-current perspectives and future directions

Padmanee Sharma¹, Sangeeta Goswami², Deblina Raychaudhuri³, Bilal A Siddiqui⁴, Pratishtha Singh³, Ashwat Nagarajan⁴, Jielin Liu⁵, Sumit K Subudhi⁴, Candice Poon⁶, Kristal L Gant⁴, Shelley M Herbrich⁴, Swetha Anandhan⁵, Shajedul Islam⁷, Moran Amit⁷, Gayathri Anandappa⁸, James P Allison⁹

Affiliations

¹ Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; The Immunotherapy Platform, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; James P. Allison Institute, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: padsharma@mdanderson.org.
² Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
³ Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁴ Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁵ Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; MD Anderson UT Health Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁶ Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁷ Department of Head & Neck Surgery Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁸ Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁹ Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; The Immunotherapy Platform, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; James P. Allison Institute, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

PMID: 37059068
DOI: 10.1016/j.cell.2023.03.006

Free article

Review

Immune checkpoint therapy-current perspectives and future directions

Padmanee Sharma et al. Cell. 2023.

Free article

. 2023 Apr 13;186(8):1652-1669.

doi: 10.1016/j.cell.2023.03.006.

Authors

Affiliations

¹ Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; The Immunotherapy Platform, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; James P. Allison Institute, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: padsharma@mdanderson.org.
² Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
³ Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁴ Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁵ Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; MD Anderson UT Health Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁶ Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁷ Department of Head & Neck Surgery Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁸ Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁹ Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; The Immunotherapy Platform, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; James P. Allison Institute, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

PMID: 37059068
DOI: 10.1016/j.cell.2023.03.006

Abstract

Immune checkpoint therapy (ICT) has dramatically altered clinical outcomes for cancer patients and conferred durable clinical benefits, including cure in a subset of patients. Varying response rates across tumor types and the need for predictive biomarkers to optimize patient selection to maximize efficacy and minimize toxicities prompted efforts to unravel immune and non-immune factors regulating the responses to ICT. This review highlights the biology of anti-tumor immunity underlying response and resistance to ICT, discusses efforts to address the current challenges with ICT, and outlines strategies to guide the development of subsequent clinical trials and combinatorial efforts with ICT.

Keywords: CTLA-4; ICT; PD-1; PD-L1; combinatorial biomarkers; cytotoxic T lymphocyte-associated protein 4; immune checkpoint therapy; immune-related adverse events; irAEs; programmed cell death protein 1; programmed death ligand 1; reverse translation.

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Conflict of interest statement

Declaration of interests P.Sharma reports consulting fees from Achelois, Adaptive Biotechnologies, Affini-T, Apricity, BioAtla, BioNTech, Candel Therapeutics, Catalio, Codiak, Constellation, Dragonfly, Earli, Enable Medicine, Glympse, Hummingbird, ImaginAb, Infinity Pharma, Jounce, JSL Health, Lava Therapeutics, Lytix, Marker, Oncolytics, PBM Capital, Phenomic AI, Polaris Pharma, Sporos, Time Bioventures, Trained Therapeutix, Two Bear Capital, and Venn Biosciences; and ownership of stocks for Achelois, Adaptive Biotechnologies, Affini-T, Apricity, BioAtla, BioNTech, Candel Therapeutics, Catalio, Codiak, Constellation, Dragonfly, Earli, Enable Medicine, Glympse, Hummingbird, ImaginAb, Infinity Pharma, Jounce, JSL Health, Lava Therapeutics, Lytix, Marker, Oncolytics, PBM Capital, Phenomic AI, Polaris Pharma, Sporos, Time Bioventures, Trained Therapeutix, Two Bear Capital, and Venn Biosciences. J.P.A. reports consulting fees from Achelois, Adaptive Biotechnologies, Apricity, BioAtla, BioNTech, Candel Therapeutics, Codiak, Dragonfly, Earli, Enable Medicine, Hummingbird, ImaginAb, Jounce, Lava Therapeutics, Lytix, Marker, PBM Capital, Phenomic AI, Polaris Pharma, Time Bioventures, Trained Therapeutix, Two Bear Capital, and Venn Biosciences; ownership of stocks for Achelois, Adaptive Biotechnologies, Apricity, BioAtla, BioNTech, Candel Therapeutics, Codiak, Dragonfly, Earli, Enable Medicine, Hummingbird, ImaginAb, Jounce, Lava Therapeutics, Lytix, Marker, PBM Capital, Phenomic AI, Polaris Pharma, Time Bioventures, Trained Therapeutix, Two Bear Capital, and Venn Biosciences.

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Immune checkpoint therapy-current perspectives and future directions

Affiliations

Immune checkpoint therapy-current perspectives and future directions

Authors

Affiliations

Abstract

Conflict of interest statement

Publication types

MeSH terms

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LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Research Materials