肿瘤微环境
癌症免疫疗法
癌症研究
髓源性抑制细胞
免疫疗法
细胞生物学
免疫
免疫系统
癌症
人口
抑制器
生物
免疫学
癌细胞
化学
医学
环境卫生
遗传学
作者
Sho Hangai,Takeshi Kawamura,Yoshitaka Kimura,Ching-Yun Chang,Sana Hibino,Daisuke Yamamoto,Yousuke Nakai,Ryosuke Tateishi,Masanobu Oshima,Hiroko Oshima,Tatsuhiko Kodama,Kyoji Moriya,Kazuhiko Koike,Hideyuki Yanai,Tadatsugu Taniguchi
标识
DOI:10.1038/s41590-021-00967-5
摘要
One of most challenging issues in tumor immunology is a better understanding of the dynamics in the accumulation of myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment (TIME), as this would lead to the development of new cancer therapeutics. Here, we show that translationally controlled tumor protein (TCTP) released by dying tumor cells is an immunomodulator crucial to full-blown MDSC accumulation in the TIME. We provide evidence that extracellular TCTP mediates recruitment of the polymorphonuclear MDSC (PMN-MDSC) population in the TIME via activation of Toll-like receptor-2. As further proof of principle, we show that inhibition of TCTP suppresses PMN-MDSC accumulation and tumor growth. In human cancers, we find an elevation of TCTP and an inverse correlation of TCTP gene dosage with antitumor immune signatures and clinical prognosis. This study reveals the hitherto poorly understood mechanism of the MDSC dynamics in the TIME, offering a new rationale for cancer immunotherapy. Cell death in the context of cancer therapies is often associated with immunogenicity. Taniguchi and colleagues instead find that release of the cellular protein TCTP following cell death triggers an immunosuppressive pathway in the tumor microenvironment.
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