Do Tumor Mechanical Stresses Promote Cancer Immune Escape?
Do Tumor Mechanical Stresses Promote Cancer Immune Escape?
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DOI：
10.3390/cells11233840
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发表时间：
2022-11-30
期刊：
影响因子：
6
通讯作者：
Datta, Meenal
中科院分区：
文献类型：
--
作者：
Onwudiwe, Killian;Najera, Julian;Siri, Saeed;Datta, Meenal
关键词：
免疫逃逸是一个公认的癌症标志，是免疫治疗有效性的主要障碍。虽然免疫逃避的分子机制和生物学后果在很大程度上是已知的，组织机械应力在这些过程中的作用值得进一步研究。肿瘤微环境（TME）的特征是物理异常（特别是TME内外施加的流体和固体压力增加），这些异常驱动癌症机制病理学。引人注目的是，响应于这些机械应力，癌细胞上调典型的免疫逃避机制，包括上皮-间充质转化（EMT）和自噬。考虑和表征TME中肿瘤机械应力的起源和后果可能会产生对抗免疫治疗耐药性的新策略。从这个角度来看，我们认为，肿瘤的机械应力，即流体剪切和固体应力诱导免疫逃避上调EMT和自噬。除了探索我们的假设的基础，我们还确定了明确的差距，需要解决的领域，以直接证明这种生物物理关系的存在和重要性。最后，我们提出，减少或中和流体剪切应力和固体应力诱导的癌症免疫逃逸可能会改善免疫治疗的结果。
Immune evasion—a well-established cancer hallmark—is a major barrier to immunotherapy efficacy. While the molecular mechanisms and biological consequences underpinning immune evasion are largely known, the role of tissue mechanical stresses in these processes warrants further investigation. The tumor microenvironment (TME) features physical abnormalities (notably, increased fluid and solid pressures applied both inside and outside the TME) that drive cancer mechanopathologies. Strikingly, in response to these mechanical stresses, cancer cells upregulate canonical immune evasion mechanisms, including epithelial–mesenchymal transition (EMT) and autophagy. Consideration and characterization of the origins and consequences of tumor mechanical stresses in the TME may yield novel strategies to combat immunotherapy resistance. In this Perspective, we posit that tumor mechanical stresses—namely fluid shear and solid stresses—induce immune evasion by upregulating EMT and autophagy. In addition to exploring the basis for our hypothesis, we also identify explicit gaps in the field that need to be addressed in order to directly demonstrate the existence and importance of this biophysical relationship. Finally, we propose that reducing or neutralizing fluid shear stress and solid stress-induced cancer immune escape may improve immunotherapy outcomes.
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