School of Mechanical Engineering and Automation, Beihang University, Beijing 100191, China.
Beijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing 100190, China.
Proc Natl Acad Sci U S A. 2024 May 28;121(22):e2322479121. doi: 10.1073/pnas.2322479121. Epub 2024 May 21.
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.
肿瘤免疫微环境中生化线索对癌症转移的影响意义重大，但微环境中物理因素的作用在很大程度上仍未得到探索。在本文中，我们研究了癌细胞与免疫细胞之间的细胞外基质（ECM）介导的机械相互作用如何影响癌细胞的免疫逃逸。我们专注于机械调节巨噬细胞对两种具有不同转移潜能的结直肠癌（CRC）细胞的靶向能力。我们的结果表明，由于癌细胞在 ECM 上表现出强烈的收缩，巨噬细胞可以有效地靶向具有低转移潜能的 CRC 细胞，而具有高转移潜能的癌细胞在 ECM 上的收缩较弱，因此可以逃避巨噬细胞的攻击以实现免疫逃逸。我们关于免疫细胞和癌细胞之间复杂机械相互作用的发现，可以为进一步探索癌症免疫治疗策略提供重要参考。
