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Decoding the Role of Interleukin-30 in the Crosstalk between Cancer and Myeloid Cells

机译:解码白介素30在癌症和髓样细胞之间的串扰中的作用

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摘要

In the last few years, a new actor hit the scene of the tumor microenvironment, the p28 subunit of interleukin (IL)-27, known as IL-30. Its molecular structure allows it to function as an autonomous cytokine and, alternatively, to pair with other subunits to form heterodimeric complexes and enables it to play different, and not fully elucidated, roles in immunity. However, data from the experimental models and clinical samples, suggest IL-30′s engagement in the relationship between cancer and myeloid cells, which fosters the tumor microenvironment and the cancer stem cell niche, boosting the disease progression. Activated myeloid cells are the primary cellular source and one of the targets of IL-30, which can also be produced by cancer cells, especially, in aggressive tumors, as observed in the breast and prostate. This review briefly reports on the immunobiology of IL-30 and related cytokines, by comparing mouse and human counterparts, and then focuses on the mechanisms whereby IL-30 amplifies intratumoral myeloid cell infiltrate and triggers a vicious cycle that worsens immunosuppression in the tumor microenvironment (TME) and constitutes a real threat for a successful immunotherapeutic strategy.
机译:在最近几年中,一个新的角色出现在肿瘤微环境中,即白介素(IL)-27的p28亚基,称为IL-30。它的分子结构使其可以充当自主细胞因子,或者与其他亚基配对以形成异二聚体复合物,并使其在免疫中发挥不同的作用,但尚未完全阐明。然而,来自实验模型和临床样品的数据表明,IL-30参与了癌症与髓样细胞之间的关系,从而促进了肿瘤微环境和癌症干细胞的发展,促进了疾病的发展。活化的髓样细胞是主要的细胞来源,也是IL-30的靶标之一,IL-30还可通过癌细胞产生,尤其是在侵袭性肿瘤中,如在乳房和前列腺中观察到的。这篇评论通过比较小鼠和人类对应物简要报道了IL-30和相关细胞因子的免疫生物学,然后重点介绍了IL-30放大肿瘤内髓样细胞浸润并触发恶性循环的机制,该恶性循环使肿瘤微环境中的免疫抑制恶化( TME)并构成成功免疫治疗策略的真正威胁。

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