Fibroblasts are a key component of the tumor microenvironment (TME) that can serve as a scaffold for tumor cell migration and augment the tumor's ability to withstand harsh conditions. When activated by external or endogenous stimuli, normal fibroblasts become cancer associated fibroblasts (CAFs), a heterogeneous group of stromal cells in the tumor that are phenotypically and epigenetically different from normal fibroblasts. Dynamic crosstalk between cancer cells, immune cells, and CAFs through chemokines and surface signaling makes the TME conducive to tumor growth. When activated, CAFs promote tumorigenesis and metastasis through several phenomena including regulation of tumor immunity, metabolic reprogramming of the TME, extracellular matrix remodeling and contraction, and induction of therapeutic resistance. Ionizing radiation (radiation theraphy [RT]) is a potent immunological stimulant that has been shown to increase cytotoxic Teff infiltration and IFN‐I stimulated genes. RT, however, is unable to overcome the infiltration and activation of immunosuppressive cells which can contribute to tumor progression. Another paradox of RT is that, while very effective at killing cancer cells, it can contribute to the formation of CAFs. This review examines how the interplay between CAFs and immune cells during RT contributes to organ fibrosis, immunosuppression, and tumor growth. We focus on targeting mechanistic pathways of CAF formation as a potentially effective strategy not only for preventing organ fibrosis, but also in hampering tumor progression in response to RT.

中文翻译：

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在放射治疗的背景下，癌症相关的成纤维细胞与免疫细胞之间的相互作用。

成纤维细胞是肿瘤微环境（TME）的关键组成部分，可作为肿瘤细胞迁移的支架并增强肿瘤抵抗恶劣条件的能力。当被外部或内源性刺激激活时，正常的成纤维细胞变成癌症相关的成纤维细胞（CAF），这是肿瘤中基质细胞的异质性组，其在表型和表观遗传学上不同于正常的成纤维细胞。癌细胞，免疫细胞和CAF之间通过趋化因子和表面信号传导之间的动态串扰使TME有利于肿瘤生长。激活后，CAFs通过多种现象促进肿瘤发生和转移，包括调节肿瘤免疫力，TME的代谢重编程，细胞外基质重塑和收缩以及诱导治疗抗性。电离辐射（辐射疗法[RT]）是一种有效的免疫刺激剂，已被证明可以增加细胞毒性Teff浸润和IFN-I刺激的基因。然而，RT不能克服免疫抑制细胞的浸润和活化，而免疫抑制细胞的浸润和活化可能有助于肿瘤的进展。RT的另一个悖论是，尽管在杀死癌细胞方面非常有效，但它可以促进CAF的形成。这篇综述探讨了RT期间CAF与免疫细胞之间的相互作用如何导致器官纤维化，免疫抑制和肿瘤生长。我们专注于靶向CAF形成的机械途径，这不仅是预防器官纤维化的一种潜在有效策略，而且还可以阻止肿瘤对RT的进展。