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The Resistance Mechanisms of Checkpoint Inhibitors in Solid Tumors

Evangelos Koustas1, Panagiotis Sarantis1, Athanasios G Papavassiliou1

  • 1Molecular Oncology Unit, Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece.

Biomolecules
|April 30, 2020
PubMed

Insights

Cancer immunotherapy offers remarkable results but faces primary and acquired resistance. This review explores resistance mechanisms and strategies to overcome them in solid tumors.

Area of Science:

  • Oncology
  • Immunology

Background:

  • Cancer immunotherapy, particularly immune checkpoint inhibitors, has transformed solid tumor treatment.
  • Despite successes, primary resistance and acquired resistance limit patient response rates.

Purpose of the Study:

  • To review the latest advancements in cancer immunotherapy.
  • To discuss the complex mechanisms underlying resistance to immunotherapy in solid tumors.
  • To explore potential therapeutic strategies for overcoming immunotherapy resistance.

Main Methods:

  • Literature review of recent studies on cancer immunotherapy and resistance.
  • Analysis of identified molecular and cellular resistance mechanisms.
  • Discussion of emerging therapeutic approaches.

Main Results:

  • Immunotherapy has shown significant clinical impact but faces challenges with patient response.
  • Multiple resistance mechanisms identified, including tumor microenvironment, autophagy, genetic/epigenetic alterations, tumor mutational burden, neo-antigens, and gut microbiota.
  • Various strategies are being developed to counteract these resistance pathways.

Conclusions:

  • Understanding resistance mechanisms is crucial for improving immunotherapy efficacy.
  • Targeting identified pathways and exploring novel strategies hold promise for overcoming resistance.
  • Further research is needed to enhance long-term patient outcomes in solid tumor immunotherapy.
Keywords:
cancerimmunotherapyresistance mechanismsolid tumors

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