BIOPIC, Beijing Advanced Innovation Center for Genomics, School of Life Sciences, Peking University, Beijing 100871, China.
Department of Hepatopancreatobiliary Surgery I, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing 100142, China.
Cell. 2021 Feb 4;184(3):792-809.e23. doi: 10.1016/j.cell.2021.01.010.
Tumor-infiltrating myeloid cells (TIMs) are key regulators in tumor progression, but the similarity and distinction of their fundamental properties across different tumors remain elusive. Here, by performing a pan-cancer analysis of single myeloid cells from 210 patients across 15 human cancer types, we identified distinct features of TIMs across cancer types. Mast cells in nasopharyngeal cancer were found to be associated with better prognosis and exhibited an anti-tumor phenotype with a high ratio of TNF/VEGFA cells. Systematic comparison between cDC1- and cDC2-derived LAMP3 cDCs revealed their differences in transcription factors and external stimulus. Additionally, pro-angiogenic tumor-associated macrophages (TAMs) were characterized with diverse markers across different cancer types, and the composition of TIMs appeared to be associated with certain features of somatic mutations and gene expressions. Our results provide a systematic view of the highly heterogeneous TIMs and suggest future avenues for rational, targeted immunotherapies.
肿瘤浸润髓系细胞(TIMs)是肿瘤进展的关键调节因子,但不同肿瘤中它们的基本特性的相似性和区别仍难以捉摸。在这里,通过对来自 15 种人类癌症类型的 210 名患者的 210 名患者的骨髓细胞进行泛癌症分析,我们确定了不同癌症类型中 TIMs 的不同特征。我们发现鼻咽癌中的肥大细胞与较好的预后相关,并表现出高 TNF/VEGFA 细胞比例的抗肿瘤表型。cDC1 和 cDC2 衍生的 LAMP3 cDC 之间的系统比较揭示了它们在转录因子和外部刺激方面的差异。此外,促血管生成的肿瘤相关巨噬细胞(TAMs)在不同癌症类型中具有不同的标志物特征,并且 TIMs 的组成似乎与某些体细胞突变和基因表达特征相关。我们的研究结果提供了对高度异质性 TIMs 的系统观点,并为合理、靶向免疫治疗提供了未来的途径。
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