Further knowledge and developments in resistance mechanisms to immune checkpoint inhibitors

Front Immunol. 2024 Jun 5:15:1384121. doi: 10.3389/fimmu.2024.1384121. eCollection 2024.

Abstract

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.

Keywords: biomarkers; cancer; checkpoint blockade; immunotherapy; resistance.

Publication types

  • Review

MeSH terms

  • Animals
  • B7-H1 Antigen / antagonists & inhibitors
  • B7-H1 Antigen / immunology
  • Drug Resistance, Neoplasm* / immunology
  • Humans
  • Immune Checkpoint Inhibitors* / therapeutic use
  • Immunotherapy / methods
  • Neoplasms* / drug therapy
  • Neoplasms* / immunology
  • Neoplasms* / therapy
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Programmed Cell Death 1 Receptor / immunology
  • Tumor Microenvironment* / immunology

Substances

  • Immune Checkpoint Inhibitors
  • B7-H1 Antigen
  • Programmed Cell Death 1 Receptor

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. LB received a fellowship from the University Côte d’Azur (Nice, France) for her PhD program. This work was supported by the “Region Provence Alpes Côte d’Azur”, “ Conseil départemental des Alpes-Maritimes”, “Association pour la Recherche contre le Cancer” (ARC Grants n° SL220110603478, ARC CANC’AIR GENExposomics and ARC Sign’it 2019), Cancéropôle PACA, Plan Cancer INSERM, FHU Oncoage, IHU RespirERA, and French national research agency (“Investments for the Future” LABEX SIGNALIFE: program reference # ANR-11-LABX-0028–01 and “STEATOX” # ANR-13-CESA-0009–01).The funding organizations had no role in the design and conduct of the study.