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The role of inflammation in the immune evasion of KRas

E Jane Homan1, Robert D Bremel1

  • 1ioGenetics LLC, Madison, WI, United States.

Frontiers in Immunology
|May 25, 2026
PubMed

Insights

Inflammation-induced cathepsin B may degrade KRas mutant neoepitopes, hiding them from immune detection. This mechanism, involving cathepsin B, trypsin, and caspases, contributes to KRas-driven tumor immune evasion.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Ras family proteins (KRas, NRas, HRas) are mutated in over 25% of human tumors, primarily at G12 or G13.
  • KRas mutations are linked to inflammation, a known tumor precursor.
  • While KRas inhibitors show promise, KRas-driven tumors often resist immunotherapy.

Purpose of the Study:

  • To investigate the impact of cathepsin B on KRas neoepitopes.
  • To elucidate the role of inflammation-associated enzymes in KRas-driven tumor immune evasion.

Main Methods:

  • Literature review of cathepsin B, trypsin, and caspase interactions.
  • Analysis of cathepsin B's effect on KRas neoepitope peptides.
  • Schematic representation of proposed immune evasion mechanisms.

Main Results:

  • Cathepsin B, upregulated in tumors, may cleave KRas G12/G13 mutant neoepitopes.
  • This cleavage could prevent neoepitope binding to MHC I, rendering them immunologically invisible.
  • Interactions with trypsin and caspases may further facilitate immune evasion.

Conclusions:

  • Cathepsin B-mediated degradation of neoepitopes is a potential mechanism for KRas tumor immune evasion.
  • Inflammation and associated enzymes play a critical role in the immune escape of Ras family-driven cancers.
Keywords:
KRascaspasecathepsinepitopeimmune evasionimmunotherapyinflammationtrypsin

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