A novel exploration of <i>COL11A1</i>'s role in regulating myeloid-derived suppressor cell activation within the colon cancer microenvironment

Wei Niu; Xiaxia Du; Yang Song; Lianyi Guo; Baohai Liu; Xin Tong

doi:10.1016/j.jpha.2024.101181

Volume 15 Issue 4

May 2025

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Wei Niu, Xiaxia Du, Yang Song, Lianyi Guo, Baohai Liu, Xin Tong. A novel exploration of COL11A1's role in regulating myeloid-derived suppressor cell activation within the colon cancer microenvironment[J]. Journal of Pharmaceutical Analysis, 2025, 15(4): 101181. doi: 10.1016/j.jpha.2024.101181

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Wei Niu, Xiaxia Du, Yang Song, Lianyi Guo, Baohai Liu, Xin Tong. A novel exploration of COL11A1's role in regulating myeloid-derived suppressor cell activation within the colon cancer microenvironment[J]. Journal of Pharmaceutical Analysis, 2025, 15(4): 101181. doi: 10.1016/j.jpha.2024.101181

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A novel exploration of COL11A1's role in regulating myeloid-derived suppressor cell activation within the colon cancer microenvironment

doi: 10.1016/j.jpha.2024.101181

a. Department of Gastroenterology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, 121000, China;
b. Department of Rehabilitation, The Third Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, 121000, China;
c. Department of Respiratory Medicine, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, 121000, China;
d. Department of General Surgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, 121000, China

Received Date: Apr. 25, 2024
Accepted Date: Dec. 29, 2024
Rev Recd Date: Dec. 05, 2024
Publish Date: Jan. 02, 2025

Abstract

Abstract

This study aimed to elucidate the role of collagen type XI alpha 1 (COL11A1)-positive cancer-associated fibroblasts (CAFs) in modifying the tumor microenvironment of colon cancer (CC) and facilitating immune evasion through interactions with myeloid-derived suppressor cells (MDSCs). Using single-cell transcriptomic sequencing, we analyzed the interplay between COL11A1-positive CAFs and MDSCs in the CC microenvironment, focusing on how COL11A1 impacts MDSC differentiation and activation. The results demonstrate that COL11A1 expression in fibroblasts significantly enhances matrix metalloproteinase (MMP)3 and MMP13 expression, leading to paracrine induction of MDSC differentiation and activation, which promotes immune evasion and tumor growth. Additionally, we observed that COL11A1 knockout (COL11A1^KO) suppresses tumor growth and hinders immune evasion. These findings underscore the essential role of COL11A1-positive CAFs in establishing an immunosuppressive tumor microenvironment conducive to CC progression. By elucidating the molecular pathway through which COL11A1 influences MDSC activity, this research suggests new therapeutic avenues for targeting the tumor microenvironment in CC, particularly through modulating COL11A1 expression in CAFs.
- Colon cancer,
- Cancer-associated fibroblasts,
- Myeloid-derived suppressor cells,
- COL11A1,
- MMP3,
- MMP13

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