Department of Medical Physics and Radiology, Faculty of Paramedical Sciences, Kashan University of Medical Sciences, Kashan, Iran.
Radiology and Nuclear Medicine Department, School of Paramedical Sciences, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Pharmacol Res. 2020 May;155:104745. doi: 10.1016/j.phrs.2020.104745. Epub 2020 Mar 4.
Emerging evidences show that changes in tumor stroma can adapt cancer cells to radiotherapy, thereby leading to a reduction in tumor response to treatment. On the other hand, radiotherapy is associated with severe reactions in normal tissues which limit the amount radiation dose received by tumor. These challenges open a window in radiobiology and radiation oncology to explore mechanisms for improving tumor response and also alleviate side effects of radiotherapy. Transforming growth factor beta (TGF-β) is a well-known and multitasking cytokine that regulates a wide range of reactions and interactions within tumor and normal tissues. Within tumor microenvironment (TME), TGF-β is the most potent suppressor of immune system activity against cancer cells. This effect is mediated through stimulation of CD4+ which differentiates to T regulatory cells (Tregs), infiltration of fibroblasts and differentiation into cancer associated fibroblasts (CAFs), and also polarization of macrophages to M2 cells. These changes lead to suppression of cytotoxic CD8 + T lymphocytes (CTLs) and natural killer (NK) cells to kill cancer cells. TGF-β also plays a key role in the angiogenesis, invasion and DNA damage responses (DDR) in cancer cells. In normal tissues, TGF-β triggers the expression of a wide range of pro-oxidant and pro-fibrosis genes, leading to fibrosis, genomic instability and some other side effects. These properties of TGF-β make it a potential target to preserve normal tissues and sensitize tumor via its inhibition. In the current review, we aim to explain the mechanisms of upregulation of TGF-β and its consequences in both tumor and normal tissues.
越来越多的证据表明，肿瘤基质的变化可以使癌细胞适应放疗，从而导致肿瘤对治疗的反应降低。另一方面，放疗会引起正常组织的严重反应，从而限制肿瘤接收到的辐射剂量。这些挑战为放射生物学和肿瘤放疗学提供了一个探索提高肿瘤反应和减轻放疗副作用的机制的窗口。转化生长因子-β（TGF-β）是一种众所周知的多功能细胞因子，可调节肿瘤和正常组织内的广泛反应和相互作用。在肿瘤微环境（TME）中，TGF-β是抑制免疫系统对癌细胞活性的最有效因子。这种作用是通过刺激 CD4+分化为调节性 T 细胞（Tregs）、成纤维细胞浸润和分化为癌相关成纤维细胞（CAFs）以及巨噬细胞向 M2 细胞极化来介导的。这些变化导致细胞毒性 CD8+T 淋巴细胞（CTLs）和自然杀伤（NK）细胞对癌细胞的杀伤作用受到抑制。TGF-β在癌细胞的血管生成、侵袭和 DNA 损伤反应（DDR）中也起着关键作用。在正常组织中，TGF-β触发一系列促氧化剂和促纤维化基因的表达，导致纤维化、基因组不稳定性和其他一些副作用。TGF-β的这些特性使其成为通过抑制它来保护正常组织和增敏肿瘤的潜在靶点。在当前的综述中，我们旨在解释 TGF-β上调及其在肿瘤和正常组织中的后果的机制。
