Analysis of the immune microenvironment in colorectal cancer with different KRAS gene subtypes

Jing Huang ¹, Qian Gong ¹, Qingshu Li ^1,2,3

¹Department of Pathology, College of Basic Medicine, Chongqing Medical University, Chongqing, 400016, China.
²Molecular Medicine Diagnostic and Testing Center, Chongqing Medical University, Chongqing, 400016, China.
³Department of Pathology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
⁴Department of Pathology, College of Basic Medicine, Chongqing Medical University, Chongqing, 400016, China. wangyalan@cqmu.edu.cn.
⁵Molecular Medicine Diagnostic and Testing Center, Chongqing Medical University, Chongqing, 400016, China. wangyalan@cqmu.edu.cn.
⁶Department of Pathology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China. wangyalan@cqmu.edu.cn.
⁷Department of Pathology, College of Basic Medicine, Chongqing Medical University, Chongqing, 400016, China. 102785@cqmu.edu.cn.
⁸Molecular Medicine Diagnostic and Testing Center, Chongqing Medical University, Chongqing, 400016, China. 102785@cqmu.edu.cn.
⁹Department of Pathology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China. 102785@cqmu.edu.cn.

⁰Department of Pathology, College of Basic Medicine, Chongqing Medical University, Chongqing, 400016, China.

Bmc Cancer +

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August 4, 2025

View abstract on PubMed

Summary

KRAS mutations in colorectal cancer influence the tumor immune microenvironment. FOXP3 regulatory T cells and M2 macrophages differ significantly between subtypes, impacting patient prognosis.

Area Of Science

Oncology
Immunology
Genetics

Background

Colorectal cancer (CRC) exhibits diverse tumor immune microenvironments (TMEs).
KRAS mutations are key drivers in CRC, influencing treatment response.
Understanding TME variations in CRC subtypes is crucial for effective immunotherapy.

Purpose Of The Study

To investigate TME differences across KRAS mutation subtypes in CRC.
To identify immune cell markers associated with KRAS phenotypes.
To guide personalized immunotherapy strategies for CRC.

Main Methods

Immunohistochemistry and panoramic scanning analyzed immune cell markers (CD8+ T cells, CD4+ T cells, NK cells, B cells, macrophages) in 55 CRC patients.
Spatial distribution and infiltration of immune cells were assessed.
TCGA and String databases correlated KRAS subtypes with immune cell markers and clinical data.

Main Results

Significant variations in immune cell infiltration and spatial distribution were observed between KRAS mutation subtypes.
FOXP3 regulatory T cells and M2 macrophages showed distinct infiltration patterns.
These cell types were strongly associated with prognosis in both KRAS wild-type and mutant CRC.

Conclusions

CRC TME complexity arises from cell-to-cell interactions and proportions, not just specific cell types.
Infiltration of FOXP3 cells and M2 macrophages likely explains KRAS mutant subtype differences.
Targeting these immune cells may offer therapeutic avenues for specific CRC subtypes.

Keywords:

FOXP3 Immune microenvironment KRAS mutation subtypes M2 macrophages