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Updated: Jan 20, 2026

Force and Position Control in Humans - The Role of Augmented Feedback
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Published on: June 19, 2016

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KRASG12/13 mutation modulates CRC outcomes via disrupting positive feedback between macrophage and CD4+ T cell

Xuehan Yan1, Juncheng Su1, Hongyuan Liu2

  • 1Department of Gastrointestinal Surgery, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.

Iscience
|January 19, 2026
PubMed

Insights

KRAS mutations in colorectal cancer disrupt immune cell interactions. Restoring CXCL9/10 with KRAS inhibitors overcomes immune suppression and controls tumor growth.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Kirsten rat sarcoma viral oncogene (KRAS) mutations are key drivers in colorectal cancer (CRC) progression.
  • The precise influence of KRAS mutations on the tumor immune microenvironment (TIME) is not fully understood.

Purpose of the Study:

  • To elucidate the impact of KRASG12/13 mutations on the TIME in colorectal cancer.
  • To identify mechanisms of immune evasion driven by KRAS mutations.
  • To propose novel therapeutic strategies for KRASG12/13-mutant CRC.

Main Methods:

  • Integration of multi-omics data from clinical CRC cohorts.
  • In vivo validation of identified mechanisms.
  • Analysis of immune cell interactions, cytokine profiles, and chemokine expression.

Main Results:

  • KRASG12/13 mutations disrupt the positive feedback loop between macrophages and CD4+ T cells.
  • Mutant tumor cells secrete increased interleukin-10 (IL-10), suppressing macrophage production of CXCL9/10 and MHC-II.
  • Impaired infiltration and activation of CXCR3+CD4+ T cells create an immunosuppressive tumor microenvironment.

Conclusions:

  • KRASG12/13 mutation drives immune evasion in CRC through IL-10-mediated suppression of macrophage chemokine and MHC-II expression.
  • Restoring CXCL9/10 levels in combination with KRAS inhibition offers a promising therapeutic approach.
  • This study provides a framework for targeting immune evasion in KRASG12/13-mutant colorectal cancer.
Keywords:
Health sciences

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