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Author Spotlight: Exploring Strategies for Successful Immune Response Against Tumors
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Author Spotlight: Exploring Strategies for Successful Immune Response Against Tumors

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Resistance to Immunotherapy: Mechanisms and Means for Overcoming

Mohamad A Salkeni1, John Y Shin2, James L Gulley3

  • 1Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD, USA. salkenima@nih.gov.

Advances in Experimental Medicine and Biology
|January 1, 2022
PubMed

Insights

Immune checkpoint blockade therapy shows promise but faces challenges with durable responses and resistance. Understanding immune escape mechanisms is key to improving cancer treatment efficacy.

Area of Science:

  • Oncology
  • Immunology
  • Cancer Therapy

Background:

  • Immune checkpoint blockade (ICB) has revolutionized cancer treatment.
  • Durable responses to ICB are not universal, with frequent early and late relapses.
  • Many patients with PD-L1-expressing tumors do not respond to PD-(L)1 blockade, indicating resistance.

Purpose of the Study:

  • To outline well-defined mechanisms of resistance to ICB.
  • To explore how tumors evade antitumor immunity.
  • To highlight strategies for overcoming primary and acquired resistance.

Main Methods:

  • Review of established mechanisms of ICB resistance.
  • Analysis of tumor-immune system interplay.
  • Identification of approaches to reinvigorate anti-tumor immunity.

Main Results:

  • Several mechanisms of primary and acquired resistance to ICB have been identified.
  • Tumors can develop adaptations to evade immune surveillance after initial response.
  • Understanding these mechanisms is crucial for therapeutic development.

Conclusions:

  • Overcoming resistance to ICB requires a deeper understanding of tumor-immune interactions.
  • Strategies to reinvigorate immunoreactivity are essential for improving patient outcomes.
  • Further research into immune escape mechanisms will guide the next generation of cancer therapies.
Keywords:
AntigenCheckpointEffectorImmunotherapyMalignancyPathwayRegulatoryResistanceSuppressor

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