A review of mechanisms of resistance to immune checkpoint inhibitors and potential strategies for therapy

Yu Fujiwara; Arjun Mittra; Abdul Rafeh Naqash; Naoko Takebe

doi:10.20517/cdr.2020.11

A review of mechanisms of resistance to immune checkpoint inhibitors and potential strategies for therapy

Cancer Drug Resist. 2020 Jun 18;3(3):252-275. doi: 10.20517/cdr.2020.11. eCollection 2020.

Authors

Yu Fujiwara^{1

2

3

4}, Arjun Mittra^{1

4}, Abdul Rafeh Naqash¹, Naoko Takebe¹

Affiliations

¹ Developmental Therapeutics Clinic, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD 20892, USA.
² Department of Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo 1358550, Japan.
³ Department of Medical Oncology, Musashino Red Cross Hospital, Tokyo 1800023, Japan.
⁴ These authors contributed equally to this work.

Abstract

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer over the last decade, bringing about a paradigm shift in systemic cancer therapy away from traditional cytotoxic and targeted therapies. While some patients have dramatic treatment responses, it is sobering to note that most tumors are either resistant at the outset, or develop resistance after initial response. A major area of translational and clinical research is in identifying therapeutic strategies to overcome resistance to ICIs. We have performed an in-depth review of the different mechanisms of resistance and potential avenues to overcome resistance through rationally designed combination treatment with ICIs.

Keywords: CTLA-4; Immunotherapy resistance; PD-1; PD-L1; tumor microenvironment.

Publication types

Review