Immune subtypes and neoantigen-related immune evasion in advanced colorectal cancer

Toshitaka Sugawara, Fuyuki Miya, Toshiaki Ishikawa, Artem Lysenko, Jo Nishino, Takashi Kamatani, Akira Takemoto, Keith A. Boroevich, Kazuhiro Kakimi, Yusuke Kinugasa, Minoru Tanabe, Tatsuhiko Tsunoda

Research output: Contribution to journalArticlepeer-review

Abstract

Elimination of cancerous cells by the immune system is an important mechanism of protection from cancer, however, its effectiveness can be reduced owing to development of resistance and evasion. To understand the systemic immune response in advanced untreated primary colorectal cancer, we analyze immune subtypes and immune evasion via neoantigen-related mechanisms. We identify a distinctive cancer subtype characterized by immune evasion and very poor overall survival. This subtype has less clonal highly expressed neoantigens and high chromosomal instability, resulting in adaptive immune resistance mediated by the immune checkpoint molecules and neoantigen presentation disorders. We also observe that neoantigen depletion caused by immunoediting and high clonal neoantigen load are correlated with a good overall survival. Our results indicate that the status of the tumor microenvironment and neoantigen composition are promising new prognostic biomarkers with potential relevance for treatment plan decisions in advanced CRC.

Original languageEnglish
Article number103740
JournaliScience
Volume25
Issue number2
DOIs
Publication statusPublished - 2022 Feb 18

Keywords

  • Genomics
  • Immune system
  • Molecular biology

ASJC Scopus subject areas

  • General

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