Deciphering and overcoming Anti-PD-1 resistance in Melanoma: A comprehensive review of Mechanisms, biomarker Developments, and therapeutic strategies

Int Immunopharmacol. 2024 May 10:132:111989. doi: 10.1016/j.intimp.2024.111989. Epub 2024 Apr 8.

Abstract

Worldwide, tens of thousands of people die from melanoma each year, making it the most frequently fatal form of cutaneous cancer. Immunotherapeutic advancements, particularly with anti-PD-1 medications, have significantly enhanced treatment outcomes over recent decades. With the broad application of anti-PD-1 therapies, insights into the mechanisms of resistance have evolved. Despite the development of combination treatments and early predictive biomarkers, a comprehensive synthesis of these advancements is absent in the current literature. This review underscores the prevailing knowledge of anti-PD-1 resistance mechanisms and underscores the critical role of robust predictive biomarkers in stratifying patients for targeted combinations of anti-PD-1 and other conventional or innovative therapeutic approaches. Additionally, we offer insights that may shape future melanoma treatment strategies.

Keywords: Anti-PD-1; Drug resistance; Immunotherapy; Melanoma.

Publication types

  • Review

MeSH terms

  • Animals
  • Biomarkers, Tumor* / metabolism
  • Drug Resistance, Neoplasm*
  • Humans
  • Immune Checkpoint Inhibitors* / pharmacology
  • Immune Checkpoint Inhibitors* / therapeutic use
  • Immunotherapy / methods
  • Melanoma* / drug therapy
  • Melanoma* / immunology
  • Programmed Cell Death 1 Receptor* / antagonists & inhibitors
  • Programmed Cell Death 1 Receptor* / metabolism
  • Skin Neoplasms* / drug therapy
  • Skin Neoplasms* / immunology

Substances

  • Programmed Cell Death 1 Receptor
  • Biomarkers, Tumor
  • Immune Checkpoint Inhibitors
  • PDCD1 protein, human