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Resistance mechanisms in melanoma to immuneoncologic therapy with checkpoint inhibitors

Sarah E Fenton1, Jeffrey A Sosman1, Sunandana Chandra1

  • 1Division of Hematology Oncology, Northwestern University, Chicago, IL 60611, USA.

Cancer Drug Resistance (Alhambra, Calif.)
|May 18, 2022
PubMed

Insights

Checkpoint inhibitors restore anti-tumor immunity but resistance is common. This review explores resistance mechanisms and strategies to improve checkpoint inhibitor efficacy in melanoma.

Area of Science:

  • Immunology
  • Oncology
  • Cancer Research

Background:

  • Checkpoint inhibitors (CPIs) harness the immune system to fight cancer by blocking immune evasion pathways.
  • CPIs have shown significant success in various cancers, including melanoma, leading to durable responses in many patients.
  • Despite initial success, primary resistance and acquired resistance to CPIs remain significant challenges, affecting the majority of patients.

Purpose of the Study:

  • To review the multifaceted mechanisms of resistance to checkpoint inhibitors in melanoma.
  • To explore potential strategies for overcoming or restoring sensitivity to checkpoint inhibitor therapy in melanoma patients.

Main Methods:

  • Literature review of studies on checkpoint inhibitor resistance in melanoma.
  • Analysis of tumor microenvironment, tumor cell intrinsic factors, and host immune cell function in resistance.
  • Synthesis of current and emerging therapeutic approaches to restore CPI sensitivity.

Main Results:

  • Resistance to CPIs involves complex interactions within the tumor microenvironment, tumor cells, and the patient's immune system.
  • Identified key mechanisms include alterations in antigen presentation, immune cell dysfunction, and immunosuppressive tumor microenvironments.
  • Emerging strategies aim to re-sensitize tumors through combination therapies and modulation of the tumor immune landscape.

Conclusions:

  • Understanding resistance mechanisms is crucial for improving CPI effectiveness in melanoma.
  • Targeting specific resistance pathways offers promising avenues for enhancing patient responses and overcoming treatment failure.
  • Future research should focus on personalized strategies to restore sensitivity and improve long-term outcomes for melanoma patients treated with CPIs.
Keywords:
Melanomacheckpoint inhibitornonresponderresistancesecondary resistance

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