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GM-CSF 通过诱导 Th9 细胞反应促进抗肿瘤免疫。

GM-CSF Promotes Antitumor Immunity by Inducing Th9 Cell Responses.

机构信息

Laboratory of Immunology, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Republic of Korea.

Department of Molecular Medicine and Biopharmaceutical Science, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Republic of Korea.

出版信息

Cancer Immunol Res. 2019 Mar;7(3):498-509. doi: 10.1158/2326-6066.CIR-18-0518. Epub 2019 Feb 6.

Abstract

GM-CSF as an adjuvant has been shown to promote antitumor immunity in mice and humans; however, the underlying mechanism of GM-CSF-induced antitumor immunity remains incompletely understood. In this study, we demonstrate that GM-CSF potentiates the efficacy of cancer vaccines through IL9-producing Th (Th9) cells. GM-CSF selectively enhanced Th9 cell differentiation by regulating the COX2-PGE pathway while inhibiting the differentiation of induced regulatory T (iTreg) cells and GM-CSF-activated monocyte-derived dendritic cells converted tumor-specific naïve Th cells into Th9 cells, and delayed tumor growth by inducing antitumor CTLs in an IL9-dependent manner. Our findings reveal a mechanism for the adjuvanticity of GM-CSF and provide a rationale for the use of GM-CSF in cancer vaccines.

摘要

GM-CSF 作为佐剂已被证明可在小鼠和人类中促进抗肿瘤免疫;然而,GM-CSF 诱导的抗肿瘤免疫的潜在机制仍不完全清楚。在这项研究中,我们证明 GM-CSF 通过产生 IL9 的 Th(Th9)细胞增强癌症疫苗的功效。GM-CSF 通过调节 COX2-PGE 途径选择性增强 Th9 细胞分化,同时抑制诱导的调节性 T(iTreg)细胞的分化,GM-CSF 激活的单核细胞衍生的树突状细胞将肿瘤特异性幼稚 Th 细胞转化为 Th9 细胞,并通过诱导依赖 IL9 的抗肿瘤 CTL 以延迟肿瘤生长。我们的研究结果揭示了 GM-CSF 佐剂作用的机制,并为 GM-CSF 在癌症疫苗中的应用提供了依据。

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