Seminars in cancer biology

Genetic factors linked to resistance to immune checkpoint blocker treatments

Updated

Abstract

Many patients do not experience a durable anti-tumor response from immune checkpoint blockers (ICB).

  • A minority of patients receiving ICB show significant and lasting benefits.
  • Resistance mechanisms to ICB are identified as both tumor-intrinsic (related to the tumor's own characteristics) and tumor-extrinsic (related to the surrounding environment).
  • The review summarizes known genetic and epigenetic factors that contribute to resistance against ICB.
  • An evaluation of the current evidence regarding these resistance mechanisms is provided.
  • Proposed therapeutic strategies aim to overcome identified resistance mechanisms.

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Full Text

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Funding

Competing interests

Declaration of Competing Interest As part of the Drug Development Department (DITEP), SC and SPV are principal investigator or sub-investigator of clinical trials from Abbvie, Agios Pharmaceuticals, Amgen, Argen-X Bvba, Arno Therapeutics, Astex Pharmaceuticals, Astra Zeneca, Aveo, Bayer Healthcare Ag, Bbb Technologies Bv, Blueprint Medicines, Boehringer Ingelheim, Bristol Myers Squibb, Celgene Corporation, Chugai Pharmaceutical Co., Clovis Oncology, Daiichi Sankyo, Debiopharm S.A., Eisai, Eli Lilly, Exelixis, Forma, Gamamabs, Genentech, Inc., Glaxosmithkline, H3 Biomedicine, Inc, Hoffmann La Roche Ag, Innate Pharma, Iris Servier, Janssen Cilag, Kyowa Kirin Pharm. Dev., Inc., Loxo Oncology, Lytix Biopharma As, Medimmune, Menarini Ricerche, Merck Sharp & Dohme Chibret, Merrimack Pharmaceuticals, Merus, Millennium Pharmaceuticals, Nanobiotix, Nektar Therapeutics, Novartis Pharma, Octimet Oncology Nv, Oncoethix, Onyx Therapeutics, Orion Pharma, Oryzon Genomics, Pfizer, Pharma Mar, Pierre Fabre, Roche, Sanofi Aventis, Taiho Pharma, Tesaro Inc, and Xencor. SPV has participated to advisory boards for Merck KGaA, has benefited from reimbursement for attending symposia from AstraZeneca and has received laboratory research funding from Fondation Roche France, Boehringher Ingelheim and Merck KGaA. RMC has no conflicts of interest or financial interests to disclose. SA is currently principal or subinvestigator as part of the department of medical oncology for clinical trials sponsored by Roche and BMS. SA has received during the past 5 years honoraria for advisory board and or presentations by Amgen, Roche, Astra Zeneca, Bristol Meyer Squib, MSD, Sanofi and Novartis.
PubMed

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