通过在肿瘤微环境（TME）中调节成纤维细胞/纤维瘢痕重塑，重用可能具有肿瘤和抗癌效应的药物，通过生化和机械传导机制，增加了化疗药物的效率，降低了药物抵抗。有趣的是，在免疫化疗后，成纤维细胞/纤维瘢痕重塑在介导癌症转移和药物抵抗中扮演着重要的角色。在诱导化疗免疫抵抗的最重要的假设是通过激活成纤维细胞/纤维瘢痕重塑和阻止T细胞浸润来阻碍主要是由于TME中细胞骨架、机械、生化、代谢、血管和重塑的信号通路之间的干扰。可以在成纤维细胞/纤维瘢痕重塑中靶向的肿瘤结构组分包括TME组分的耗竭、针对癌相关成纤维细胞和肿瘤相关巨噬细胞、减轻基质内的机械应力以及正常化血管。还发现，在免疫化疗过程中，TME损伤和成纤维细胞/纤维瘢痕重塑会导致抑制信号上调和激活信号下调，从而导致肿瘤的免疫逃逸或化疗抵抗。在这方面，通过包括抗纤颤效应在内的多种传导信号机制的重用或新辅助药物被用于靶向TME和成纤维细胞/纤维瘢痕信号通路，如血管紧张素2、转化生长因子-beta、TME的物理障碍、细胞因子和代谢因子，最终导致化疗抵抗的逆转。许多重用药物，如吡非尼酮、二甲双胍、洛沙坦、曲尼那酯、地塞米松和利血平，被用于通过消除TME抑制信号来降低免疫抑制，刺激免疫系统，增加化疗药物的效率并减少抵抗。为了克服基于成纤维细胞/纤维瘢痕重塑的免疫抑制，在这篇综述中，我们着重于抑制信号传导，即物理屏障，减轻机械应力并防止机械代谢激活。版权所有 © 2023. 由Elsevier B.V.出版。

The use of repurposing drugs that may have neoplastic and anticancer effects increases the efficiency and decrease resistance to chemotherapy drugs through a biochemical and mechanical transduction mechanisms through modulation of fibroblast/fibrosis remodeling in tumor microenvironment (TME). Interestingly, fibroblast/fibrosis remodeling plays a vital role in mediating cancer metastasis and drug resistance after immune chemotherapy. The most essential hypothesis for induction of chemo-immunotherapy resistance is via activation of fibroblast/fibrosis remodeling and preventing the infiltration of T cells after is mainly due to the interference between cytoskeleton, mechanical, biochemical, metabolic, vascular, and remodeling signaling pathways in TME. The structural components of the tumor that can be targeted in the fibroblast/fibrosis remodeling include the depletion of the TME components, targeting the cancer-associated fibroblasts and tumor associated macrophages, alleviating the mechanical stress within the ECM, and normalizing the blood vessels. It has also been found that during immune-chemotherapy, TME injury and fibroblast/fibrosis remodeling causes the up-regulation of inhibitory signals and down-regulation of activated signals, which results in immune escape or chemo-resistance of the tumor. In this regard, repurposing or neo-adjuvant drugs with various transduction signaling mechanisms, including anti-fibrotic effects, are used to target the TME and fibroblast/fibrosis signaling pathway such as angiotensin 2, transforming growth factor-beta, physical barriers of the TME, cytokines and metabolic factors which finally led to the reverse of the chemo-resistance. Consistent to many repurposing drugs such as pirfenidone, metformin, losartan, tranilast, dexamethasone and pentoxifylline are used to decrease immune-suppression by abrogation of TME inhibitory signal that stimulates the immune system and increases efficiency and reduces resistance to chemotherapy drugs. To overcome immunosuppression based on fibroblast/fibrosis remodeling, in this review, we focus on inhibitory signal transduction, which is the physical barrier, alleviates mechanical stress and prevents mechano-metabolic activation.Copyright © 2023. Published by Elsevier B.V.