Ovarian cancer mutational processes drive site-specific immune evasion

Abstract High-grade serous ovarian cancer (HGSOC) is an archetypal cancer of genomic instability 1–4 patterned by distinct mutational processes 5,6 , tumour heterogeneity 7–9 and intraperitoneal spread 7,8,10 . Immunotherapies have had limited efficacy in HGSOC 11–13 , highlighting an unmet need to assess how mutational processes and the anatomical sites of tumour foci determine the immunological states of the tumour microenvironment. Here we carried out an integrative analysis of whole-genome sequencing, single-cell RNA sequencing, digital histopathology and multiplexed immunofluorescence of 160 tumour sites from 42 treatment-naive patients with HGSOC. Homologous recombination-deficient HRD-Dup ( BRCA1…

• UD
  U.S. Department of Defense

  Awards: W81XWH, OC150111
• BC
  Breast Cancer Research Foundation
• MS
  Memorial Sloan-Kettering Cancer Center

  Awards: CA008748, P30-CA008748
• OC
  Ovarian Cancer Research Alliance
• CF
  Cycle for Survival

  Award: P30-CA008748
• CR
  Cancer Research UK

  Award: C42358/A27460
• NI
  National Institutes of Health

  Awards: NIH T32, W81XWH, CA247749-01, CA184746, P30-CA008748
• MA
  Marie-Josée and Henry R. Kravis Center for Molecular Oncology

  Award: P30-CA008748
• NC
  National Cancer Institute

  Awards: P50-CA247749, CA247749, CA008748, P30-CA008748, CA184746
• CD
  Congressionally Directed Medical Research Programs

  Award: OC150111