In most tumors, cancer cells show the ability to dynamically transit from a non-cancer stem-like cell to a cancer stem-like cell (CSC) state and vice versa. This cell plasticity has been associated with the epithelial-to-mesenchymal transition program (EMT) and can be regulated by tumor cell-intrinsic mechanisms and complex interactions with various tumor microenvironment (TME) components. These interactions favor the generation of a specific “CSC niche” that helps maintain the main properties, phenotypic plasticity and metastatic potential of this subset of tumor cells. For this reason, TME has been recognized as an important promoter of tumor progression and therapy resistance. Tumors have evolved a network of immunosuppressive mechanisms that limits the cytotoxic T cell response to cancer cells. Some key players in this network are tumor-associated macrophages, myeloid-derived suppressor cells and regulatory T cells, which not only favor a pro-tumoral and immunosuppressive environment that supports tumor growth and immune evasion, but also negatively influences immunotherapy. Here, we review the relevance of cytokines and growth factors provided by immunosuppressive immune cells in regulating cancer-cell plasticity. We also discuss how cancer cells remodel their own niche to promote proliferation, stemness and EMT, and escape immune surveillance. A better understanding of CSC-TME crosstalk signaling will enable the development of effective targeted or immune therapies that block tumor growth and metastasis.

中文翻译：

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肿瘤浸润性免疫抑制细胞在癌细胞可塑性，肿瘤进展和治疗反应中的作用。

在大多数肿瘤中，癌细胞显示出从非癌症干细胞样状态动态转变为癌症干细胞样状态（CSC）的能力，反之亦然。这种细胞可塑性已经与上皮到间质转化程序（EMT）相关联，并且可以通过肿瘤细胞内在机制以及与各种肿瘤微环境（TME）成分的复杂相互作用来调节。这些相互作用有利于产生特定的“ CSC利基”，从而有助于维持这一肿瘤细胞子集的主要特性，表型可塑性和转移潜力。因此，TME被公认为是肿瘤进展和治疗抗性的重要促进剂。肿瘤已经形成了一种免疫抑制机制网络，该机制限制了细胞毒性T细胞对癌细胞的反应。该网络中的一些关键参与者是肿瘤相关的巨噬细胞，髓样来源的抑制细胞和调节性T细胞，它们不仅有利于支持肿瘤生长和免疫逃逸的促肿瘤和免疫抑制环境，而且会对免疫疗法产生负面影响。在这里，我们审查了免疫抑制性免疫细胞在调节癌细胞可塑性中提供的细胞因子和生长因子的相关性。我们还讨论了癌细胞如何重塑自身的生态位以促进增殖，干性和EMT，并逃避免疫监视。对CSC-TME串扰信号的更好理解将有助于开发有效的靶向或免疫疗法，从而阻断肿瘤的生长和转移。这不仅有利于支持肿瘤生长和免疫逃逸的促肿瘤和免疫抑制环境，而且对免疫治疗产生负面影响。在这里，我们审查了免疫抑制性免疫细胞在调节癌细胞可塑性中提供的细胞因子和生长因子的相关性。我们还讨论了癌细胞如何重塑自身的生态位以促进增殖，干性和EMT，并逃避免疫监视。对CSC-TME串扰信号的更好理解将有助于开发有效的靶向或免疫疗法，从而阻断肿瘤的生长和转移。这不仅有利于支持肿瘤生长和免疫逃逸的促肿瘤和免疫抑制环境，而且对免疫治疗产生负面影响。在这里，我们审查了免疫抑制性免疫细胞在调节癌细胞可塑性中提供的细胞因子和生长因子的相关性。我们还讨论了癌细胞如何重塑自身的生态位以促进增殖，干性和EMT，并逃避免疫监视。对CSC-TME串扰信号的更好理解将有助于开发有效的靶向或免疫疗法，从而阻断肿瘤的生长和转移。我们还讨论了癌细胞如何重塑自身的生态位以促进增殖，干性和EMT，并逃避免疫监视。对CSC-TME串扰信号的更好理解将有助于开发有效的靶向或免疫疗法，从而阻断肿瘤的生长和转移。我们还讨论了癌细胞如何重塑自身的生态位以促进增殖，干性和EMT，并逃避免疫监视。对CSC-TME串扰信号的更好理解将有助于开发有效的靶向或免疫疗法，从而阻断肿瘤的生长和转移。