IL-17 在癌症中的免疫反应是有争议的，观察到肿瘤促进和肿瘤抑制作用。为了阐明 IL-17 信号传导在癌症进展中的作用，我们使用了来自不同组织来源的同基因肿瘤模型。我们发现宿主IL-17RA或IL-17A/F表达缺陷对不同实体瘤（包括黑色素瘤、肉瘤、淋巴瘤和白血病）的体内生长有不同的影响。在每种肿瘤类型中，IL-17的缺失都会导致肿瘤微环境中与炎症和转移相关的介质表达发生变化。此外，宿主中 IL-17 信号传导缺陷导致抗肿瘤 CD8 T 细胞免疫力下降，并导致几种淋巴细胞群发生肿瘤特异性变化。我们的发现与注射的肿瘤细胞系中 IL-17A/F 细胞因子和受体亚基表达的不同模式相关。这些模式影响肿瘤细胞对 IL-17 和下游细胞内信号传导的反应，从而对癌症进展产生不同的影响。此外，我们确定 IL-17RC 是肿瘤细胞中 IL-17 介导的反应的关键决定因素，也是肿瘤进展中 IL-17 信号传导作用的潜在生物标志物。我们的研究深入了解了癌症中 IL-17 活性的分子机制，并为开发个性化免疫疗法奠定了基础。© 2023 作者。经泰勒许可出版

IL-17 immune responses in cancer are controversial, with both tumor-promoting and tumor-repressing effects observed. To clarify the role of IL-17 signaling in cancer progression, we used syngeneic tumor models from different tissue origins. We found that deficiencies in host IL-17RA or IL-17A/F expression had varying effects on the in vivo growth of different solid tumors including melanoma, sarcoma, lymphoma, and leukemia. In each tumor type, the absence of IL-17 led to changes in the expression of mediators associated with inflammation and metastasis in the tumor microenvironment. Furthermore, IL-17 signaling deficiencies in the hosts resulted in decreased anti-tumor CD8+ T cell immunity and caused tumor-specific changes in several lymphoid cell populations. Our findings were associated with distinct patterns of IL-17A/F cytokine and receptor subunit expression in the injected tumor cell lines. These patterns affected tumor cell responsiveness to IL-17 and downstream intracellular signaling, leading to divergent effects on cancer progression. Additionally, we identified IL-17RC as a critical determinant of the IL-17-mediated response in tumor cells and a potential biomarker for IL-17 signaling effects in tumor progression. Our study offers insight into the molecular mechanisms underlying IL-17 activities in cancer and lays the groundwork for developing personalized immunotherapies.© 2023 The Author(s). Published with license by Taylor & Francis Group, LLC.