根据癌症细胞中IL-17受体亚基表达模式,白细胞介素-17信号影响CD8+T细胞免疫和肿瘤进展。

IF 7.2 2区 医学
Oncoimmunology Pub Date : 2023-10-05 eCollection Date: 2023-01-01 DOI:10.1080/2162402X.2023.2261326
Constanza Rodriguez, Cintia L Araujo Furlan, Jimena Tosello Boari, Sabrina N Bossio, Santiago Boccardo, Laura Fozzatti, Fernando P Canale, Cristian G Beccaria, Nicolás G Nuñez, Danilo G Ceschin, Eliane Piaggio, Adriana Gruppi, Carolina L Montes, Eva V Acosta Rodríguez
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引用次数: 0

摘要

癌症中的IL-17免疫反应是有争议的,观察到了促进肿瘤和抑制肿瘤的作用。为了阐明IL-17信号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表达不足对不同实体瘤的体内生长有不同的影响,包括黑色素瘤、肉瘤、淋巴瘤和白血病。在每种肿瘤类型中,IL-17的缺失导致肿瘤微环境中与炎症和转移相关的介质的表达发生变化。此外,宿主中IL-17信号传导缺陷导致抗肿瘤CD8+T细胞免疫力降低,并导致几个淋巴细胞群中的肿瘤特异性变化。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有关。这些模式影响肿瘤细胞对IL-17的反应性和下游细胞内信号传导,导致对癌症进展的不同影响。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。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Interleukin-17 signaling influences CD8<sup>+</sup> T cell immunity and tumor progression according to the IL-17 receptor subunit expression pattern in cancer cells.

Interleukin-17 signaling influences CD8<sup>+</sup> T cell immunity and tumor progression according to the IL-17 receptor subunit expression pattern in cancer cells.

Interleukin-17 signaling influences CD8<sup>+</sup> T cell immunity and tumor progression according to the IL-17 receptor subunit expression pattern in cancer cells.

Interleukin-17 signaling influences CD8+ T cell immunity and tumor progression according to the IL-17 receptor subunit expression pattern in cancer cells.

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.

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来源期刊
Oncoimmunology
Oncoimmunology ONCOLOGY-IMMUNOLOGY
CiteScore
12.80
自引率
2.80%
发文量
276
期刊介绍: Tumor immunology explores the natural and therapy-induced recognition of cancers, along with the complex interplay between oncogenesis, inflammation, and immunosurveillance. In response to recent advancements, a new journal, OncoImmunology, is being launched to specifically address tumor immunology. The field has seen significant progress with the clinical demonstration and FDA approval of anticancer immunotherapies. There's also growing evidence suggesting that many current chemotherapeutic agents rely on immune effectors for their efficacy. While oncologists have historically utilized chemotherapeutic and radiotherapeutic regimens successfully, they may have unwittingly leveraged the immune system's ability to recognize tumor-specific antigens and control cancer growth. Consequently, immunological biomarkers are increasingly crucial for cancer prognosis and predicting chemotherapy efficacy. There's strong support for combining conventional anticancer therapies with immunotherapies. OncoImmunology will welcome high-profile submissions spanning fundamental, translational, and clinical aspects of tumor immunology, including solid and hematological cancers, inflammation, and both innate and acquired immune responses.
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