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A mutational signature and significantly mutated driver genes associated with immune checkpoint inhibitor response

Qinghua Wang1, Wenjing Zhang1, Yuxian Guo1

  • 1Department of Health Statistics, Key Laboratory of Medicine and Health of Shandong Province, School of Public Health, Weifang Medical University, Weifang, Shandong 261053, China.

International Immunopharmacology
|February 8, 2023
PubMed

Insights

Identifying new biomarkers can predict which patients benefit from immune checkpoint inhibitors (ICIs) in advanced cancers. Specific mutations and molecular subtypes indicate better responses to immunotherapy, guiding personalized cancer treatment.

Area of Science:

  • Oncology
  • Immunology
  • Genetics

Background:

  • Immune checkpoint inhibitors (ICIs) improve survival in advanced cancers.
  • Only a subset of patients respond to ICI therapy, necessitating predictive biomarkers.

Purpose of the Study:

  • To identify novel molecular biomarkers for predicting immunotherapy efficacy across multiple cancer types.
  • To analyze somatic mutational profiles and clinical data for predictive insights.

Main Methods:

  • Analysis of pre-treatment somatic mutational profiles from 1097 cancer samples (melanoma, NSCLC, ccRCC, BLCA, HNSCC).
  • Determination of mutational signatures, molecular subtypes, and significantly mutated genes (SMGs).
  • Evaluation of associations between molecular features and ICI response/outcomes.

Main Results:

  • Six mutational signatures were identified; one (T>C substitutions) correlated with ICI resistance.
  • A molecular subtype based on mutational activity showed improved ICI response and outcomes.
  • Mutations in COL11A1 or COL4A6 were associated with superior ICI treatment efficacy.

Conclusions:

  • Novel molecular determinants of cancer immunotherapy response were uncovered in a multi-cancer setting.
  • Findings provide insights for patient selection and personalized treatment strategies for immunotherapy.
Keywords:
Clinical biomarkersImmune checkpoint inhibitorMolecular subtypeMutational signaturesPan-cancerSMGs

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