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Role of natural and adaptive immunity in renal cell carcinoma response to VEGFR-TKIs and mTOR inhibitor

机译:自然和适应性免疫在肾细胞癌对VEGFR-TKI和mTOR抑制剂的应答中的作用

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摘要

Angiogenesis and immunosuppression work hand-in-hand in the renal cell carcinoma (RCC) microenvironment. Tumor growth is associated with impaired antitumor immune response in RCC, which involves T cells, natural killer cells, dendritic cells (DCs) and macrophages. Vascular endothelial growth factor receptor (VEGFR), such as sorafenib, sunitinib, pazopanib and axitinib, and mammalian target of rapamycin (mTOR) inhibitors, such as temsirolimus and everolimus, do exert both antiangiogenic and immunomodulatory functions. Indeed, these agents affect neutrophil migration, as well as T lymphocyte-DC cross-talk, DC maturation and immune cell metabolism and reactivity. In this review, we overview the essential role of innate and adaptive immune response in RCC proliferation, invasion and metastasis and the relationship between tumor-associated immune cells and the response to targeted agents approved for the treatment of metastatic RCC.
机译:血管生成和免疫抑制在肾细胞癌(RCC)微环境中协同工作。肿瘤生长与RCC中抗肿瘤免疫反应受损有关,RCC涉及T细胞,自然杀伤细胞,树突状细胞(DC)和巨噬细胞。血管内皮生长因子受体(VEGFR),例如索拉非尼,舒尼替尼,帕唑帕尼和阿西替尼,以及哺乳动物雷帕霉素(mTOR)抑制剂的靶标,例如西罗莫司和依维莫司,确实具有抗血管生成和免疫调节功能。实际上,这些试剂影响嗜中性粒细胞迁移,以及T淋巴细胞-DC串扰,DC成熟以及免疫细胞代谢和反应性。在这篇综述中,我们概述了先天性和适应性免疫应答在RCC增殖,侵袭和转移中的重要作用,以及肿瘤相关免疫细胞与对已批准用于治疗转移性RCC的靶向药物的应答之间的关系。

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