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Debugging the Black Box

James C Yang1

  • 1Surgery Branch, National Cancer Institute, Bethesda, Maryland. JamesYang@mail.nih.gov.

Cancer Discovery
|March 8, 2017
PubMed

Insights

Cancer immunotherapies can fail when tumors lose their most immunogenic mutations during checkpoint blockade treatment. Understanding this mechanism is key to improving cancer treatment effectiveness and patient outcomes.

Area of Science:

  • Oncology
  • Immunology
  • Cancer Research

Background:

  • Improving cancer immunotherapies requires a deeper understanding of tumor rejection mechanisms.
  • Tumor progression and treatment resistance are complex processes influenced by genetic alterations.

Purpose of the Study:

  • To investigate the relationship between tumor immunogenicity and mutations during cancer progression.
  • To identify mechanisms of resistance to immune checkpoint blockade therapy.

Main Methods:

  • Analysis of tumor mutations in patients undergoing checkpoint blockade.
  • Prediction of mutation immunogenicity using computational methods.

Main Results:

  • Mutations predicted to be highly immunogenic were preferentially lost during cancer progression.
  • Loss of immunogenic mutations correlated with treatment failure in some patients.

Conclusions:

  • Tumor evolution under immune pressure can lead to the loss of targets for immunotherapy.
  • Strategies to overcome this resistance mechanism are needed to enhance the efficacy of cancer immunotherapies.

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