Single-cell dissection of cellular components and interactions shaping the tumor immune phenotypes in ovarian cancer
Single-cell dissection of cellular components and interactions shaping the tumor immune phenotypes in ovarian cancer
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DOI：
10.1016/j.ccell.2021.04.004
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发表时间：
2021-07-12
期刊：
影响因子：
50.3
通讯作者：
Wang, Yulei
中科院分区：
文献类型：
--
作者：
Hornburg, Milena;Desbois, Melanie;Wang, Yulei
不同的T细胞浸润模式，即，免疫浸润、排斥和消失导致对癌症免疫疗法的不同应答。然而，支撑这些肿瘤免疫表型的关键决定因素和生物学仍然难以捉摸。在这里，我们通过对15个卵巢肿瘤的单细胞RNA测序分析，提供了整个肿瘤生态系统的高分辨率解剖。免疫沙漠肿瘤的特征在于独特的肿瘤细胞内在特征，包括代谢途径和低抗原呈递，以及单核细胞和未成熟巨噬细胞的富集。免疫浸润和免疫排斥的肿瘤在T细胞组成和成纤维细胞亚群方面有显著差异。此外，我们的研究揭示了区室内和跨区室的趋化因子受体-配体相互作用作为介导免疫细胞浸润的潜在机制，例如通过CXCL 16-CXCR 6的肿瘤细胞-T细胞串扰和通过CXCL 12/14-CXCR 4的基质-免疫细胞串扰。我们的数据突出了塑造肿瘤免疫表型的潜在分子机制，并可能为改善癌症免疫疗法的临床益处的治疗策略提供信息。
Distinct T cell infiltration patterns, i.e., immune infiltrated, excluded, and desert, result in different responses to cancer immunotherapies. However, the key determinants and biology underpinning these tumor immune phenotypes remain elusive. Here, we provide a high-resolution dissection of the entire tumor ecosystem through single-cell RNA-sequencing analysis of 15 ovarian tumors. Immune-desert tumors are characterized by unique tumor cell-intrinsic features, including metabolic pathways and low antigen presentation, and an enrichment of monocytes and immature macrophages. Immune-infiltrated and -excluded tumors differ markedly in their T cell composition and fibroblast subsets. Furthermore, our study reveals chemokine receptor-ligand interactions within and across compartments as potential mechanisms mediating immune cell infiltration, exemplified by the tumor cell-T cell cross talk via CXCL16-CXCR6 and stromal-immune cell cross talk via CXCL12/14-CXCR4. Our data highlight potential molecular mechanisms that shape the tumor immune phenotypes and may inform therapeutic strategies to improve clinical benefit from cancer immunotherapies.