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Immune selection determines tumor antigenicity and influences response to checkpoint inhibitors

Luis Zapata1, Giulio Caravagna2,3, Marc J Williams4

  • 1Centre for Evolution and Cancer, The Institute of Cancer Research, London, UK. luis.zapata@icr.ac.uk.

Nature Genetics
|March 9, 2023
PubMed

Insights

Cancer evolution shapes tumor immunity. Researchers used immune dN/dS to classify tumors as immune-edited or immune-escaped, finding immune-escaped tumors respond best to immunotherapy, unlike immune-edited ones.

Area of Science:

  • Oncology
  • Immunology
  • Evolutionary Biology

Background:

  • Cancer cells evolve to evade immune detection.
  • Immune selection pressure influences tumor progression and treatment response.

Purpose of the Study:

  • To develop a method for quantifying immune selection pressure in tumors.
  • To differentiate between immune-edited and immune-escaped tumors.
  • To predict immunotherapy response based on immune editing status.

Main Methods:

  • Analysis of >10,000 primary tumors and 356 immunotherapy-treated metastases.
  • Calculation of immune dN/dS (ratio of nonsynonymous to synonymous mutations in the immunopeptidome).
  • Classification of tumors into immune-edited and immune-escaped categories based on selection signatures.

Main Results:

  • Immune-edited tumors showed negative selection on antigenic mutations and CD8 T cell infiltration.
  • Immune-escaped tumors were associated with aberrant immune modulation.
  • Immune-escaped metastases responded better to immune-checkpoint blockade than immune-edited tumors.
  • Nivolumab treatment removed neoantigens in non-immune-edited patients, correlating with better survival.

Conclusions:

  • Immune dN/dS is a valuable metric for assessing immune selection in cancer.
  • Tumor immune editing status can predict response to immune-checkpoint inhibitors.
  • Distinguishing between immune-edited and immune-escaped tumors aids in personalized cancer therapy strategies.

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