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

Toshitaka Sugawara1, Fuyuki Miya2,3,4,5, Toshiaki Ishikawa6

  • 1Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan.

Iscience
|February 7, 2022
PubMed

Insights

Researchers identified a colorectal cancer subtype with immune evasion and poor survival, linked to low neoantigens and high chromosomal instability. Tumor microenvironment and neoantigen status may guide treatment for advanced colorectal cancer (CRC).

Area of Science:

  • Immunology
  • Oncology
  • Genetics

Background:

  • The immune system protects against cancer, but cancer cells can develop resistance and evade immune detection.
  • Understanding the immune response in advanced colorectal cancer (CRC) is crucial for improving patient outcomes.
  • Neoantigens, arising from tumor-specific mutations, are key targets for anti-cancer immunity.

Purpose of the Study:

  • To investigate immune subtypes and neoantigen-related immune evasion mechanisms in advanced, untreated primary colorectal cancer.
  • To identify potential prognostic biomarkers for advanced CRC based on immune status and neoantigen composition.

Main Methods:

  • Analysis of immune subtypes and immune evasion in advanced CRC patient samples.
  • Examination of neoantigen load, chromosomal instability, and immune checkpoint molecule expression.
  • Correlation of tumor microenvironment and neoantigen characteristics with overall survival.

Main Results:

  • A distinct CRC subtype characterized by immune evasion and poor overall survival was identified.
  • This poor-prognosis subtype exhibited fewer highly expressed neoantigens and high chromosomal instability, leading to adaptive immune resistance.
  • Immunoediting-induced neoantigen depletion and high clonal neoantigen load were associated with better overall survival.

Conclusions:

  • Tumor microenvironment status and neoantigen composition are significant factors in advanced CRC prognosis.
  • These factors represent promising novel prognostic biomarkers.
  • Findings may inform treatment plan decisions for advanced colorectal cancer patients.
Keywords:
GenomicsImmune systemMolecular biology

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