Further knowledge and developments in resistance mechanisms to immune checkpoint inhibitors.

The past decade has witnessed a revolution in cancer treatment, shifting from conventional drugs (chemotherapies) towards targeted molecular therapies and immune-based therapies, in particular immune-checkpoint inhibitors (ICIs). These immunotherapies release the host's immune system against the tumor and have shown unprecedented durable remission for patients with cancers that were thought incurable, such as metastatic melanoma, metastatic renal cell carcinoma (RCC), microsatellite instability (MSI) high colorectal cancer and late stages of non-small cell lung cancer (NSCLC). However, about 80% of the patients fail to respond to these immunotherapies and are therefore left with other less effective and potentially toxic treatments. Identifying and understanding the mechanisms that enable cancerous cells to adapt to and eventually overcome therapy can help circumvent resistance and improve treatment. In this review, we describe the recent discoveries on the onco-immunological processes which govern the tumor microenvironment and their impact on the resistance to PD-1/PD-L1 checkpoint blockade.
Competing Interests: MI has received honoraria for travel support and consulting/advisory roles for AstraZeneca, Bristol-Myers Squibb, Roche, Boehringer-Ingelheim and Merck & Co. outside the submitted work. PH has received honoraria for travel support and consulting/advisory roles for AstraZeneca, Roche, Bristol-Myers Squibb, Novartis, Pfizer, MSD, Qiagen, Thermo-Fisher Scientist, Janssen, Abbvie, Biocartis, Pierre Fabre, Sanofi, and Merck & Co. outside the submitted work. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2024 Berland, Gabr, Chang, Ilié, Hofman, Rignol, Ghiringhelli, Mograbi, Rashidian and Hofman.)