Physical immune escape: Weakened mechanical communication leads to escape of metastatic colorectal carcinoma cells from macrophages

The significance of biochemical cues in the tumor immune microenvironment in affecting cancer metastasis is well established, but the role of physical factors in the microenvironment remains largely unexplored. In this article, we investigated how the mechanical interaction between cancer cells and...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2024-05, Vol.121 (22), p.e2322479121-e2322479121
Main Authors: Yang, Chen, Dong, Xinrui, Sun, Bingrui, Cao, Ting, Xie, Ruipei, Zhang, Yiyu, Yang, Ziyue, Huang, Jing, Lu, Ying, Li, Ming, Wang, Xiaochen, Xu, Ye, Ye, Fangfu, Fan, Qihui
Format: Article
Language:English
Subjects:
Animals
Cancer
Cancer immunotherapy
Cell Communication - immunology
Cell interactions
Cell Line, Tumor
Colorectal carcinoma
Colorectal Neoplasms - immunology
Colorectal Neoplasms - pathology
Extracellular matrix
Extracellular Matrix - immunology
Extracellular Matrix - metabolism
Humans
Immune evasion
Immune system
Immunotherapy
Macrophages
Macrophages - immunology
Mechanical stimuli
Metastases
Metastasis
Mice
Microenvironments
Neoplasm Metastasis
Physical factors
Physical Sciences
Tumor Escape
Tumor Microenvironment - immunology
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Summary:The significance of biochemical cues in the tumor immune microenvironment in affecting cancer metastasis is well established, but the role of physical factors in the microenvironment remains largely unexplored. In this article, we investigated how the mechanical interaction between cancer cells and immune cells, mediated by extracellular matrix (ECM), influences immune escape of cancer cells. We focus on the mechanical regulation of macrophages' targeting ability on two distinct types of colorectal carcinoma (CRC) cells with different metastatic potentials. Our results show that macrophages can effectively target CRC cells with low metastatic potential, due to the strong contraction exhibited by the cancer cells on the ECM, and that cancer cells with high metastatic potential demonstrated weakened contractions on the ECM and can thus evade macrophage attack to achieve immune escape. Our findings regarding the intricate mechanical interactions between immune cells and cancer cells can serve as a crucial reference for further exploration of cancer immunotherapy strategies.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.2322479121