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Resistance to anticancer immunity in cancer patients: potential strategies to reverse resistance

B Bonavida1, S Chouaib2

  • 1Department of Microbiology, Immunology and Molecular Genetics, Jonsson Comprehensive Cancer Center and David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, USA.

Annals of Oncology : Official Journal of the European Society for Medical Oncology
|November 20, 2016
PubMed

Insights

Cancer immunotherapies show promise, but resistance is a challenge. This review explores mechanisms of cancer resistance to immunotherapy and strategies to overcome it by targeting tumors and their microenvironment.

Area of Science:

  • Oncology
  • Immunology
  • Cancer Research

Background:

  • Immunotherapy has revolutionized cancer treatment, yielding significant responses in advanced malignancies.
  • Early approaches focused on T cell-mediated cytotoxicity, evolving to antibody-mediated therapies with over 25 FDA-approved agents.
  • Despite successes, a notable subset of patients exhibits primary or acquired resistance to immunotherapy.

Purpose of the Study:

  • To review documented instances of cancer resistance to immunotherapy.
  • To elucidate the mechanisms underlying immunotherapy resistance.
  • To discuss strategies for overcoming resistance by targeting tumor cells and the tumor microenvironment.

Main Methods:

  • Literature review of immunotherapy applications in cancer.
  • Analysis of mechanisms driving resistance to T cell- and antibody-based therapies.
  • Examination of therapeutic strategies targeting tumor cell-intrinsic and microenvironmental factors.

Main Results:

  • Immunotherapy, including T cell and antibody therapies, can elicit substantial clinical responses with low toxicity.
  • A significant proportion of patients do not respond to immunotherapy or develop resistance after initial benefit.
  • Mechanisms of resistance involve direct tumor cell alterations and modulation of the tumor microenvironment.

Conclusions:

  • Cancer resistance to immunotherapy is a clinically relevant phenomenon.
  • Targeting tumor cells directly and/or their microenvironment offers promising avenues to overcome resistance.
  • Further research into resistance mechanisms and novel therapeutic strategies is crucial for improving patient outcomes.
Keywords:
cancercheckpoint inhibitorscytotoxic T cellsimmunotherapyovercoming resistance

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