Diverse immune response of DNA damage repair-deficient tumors

Tao Qing, Tomi Jun, Katherine E. Lindblad, Amaia Lujambio, Michal Marczyk, Lajos Pusztai, Kuan lin Huang

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Tumors with DNA damage repair (DDR) deficiency accumulate genomic alterations that may serve as neoantigens and increase sensitivity to immune checkpoint inhibitor. However, over half of DDR-deficient tumors are refractory to immunotherapy, and it remains unclear which mutations may promote immunogenicity in which cancer types. We integrate deleterious somatic and germline mutations and methylation data of DDR genes in 10,080 cancers representing 32 cancer types and evaluate the associations of these alterations with tumor neoantigens and immune infiltrates. Our analyses identify DDR pathway mutations that are associated with higher neoantigen loads, adaptive immune markers, and survival outcomes of immune checkpoint inhibitor-treated animal models and patients. Different immune phenotypes are associated with distinct types of DDR deficiency, depending on the cancer type context. The comprehensive catalog of immune response-associated DDR deficiency may explain variations in immunotherapy outcomes across DDR-deficient cancers and facilitate the development of genomic biomarkers for immunotherapy.

Original languageEnglish
Article number100276
JournalCell Reports Medicine
Issue number5
StatePublished - 18 May 2021


  • DNA damage repair deficiency
  • germline variant
  • immune checkpoint inhibitor
  • immune infiltrate
  • immunogenicity
  • methylation
  • mismatch repair
  • neoantigen
  • somatic mutations
  • tumor mutation burden


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