原发性和转移性肿瘤中克隆性扩增的EOMES+ Tr1样细



  Clonally expanded EOMES+ Tr1-like cells in primary and metastatic tumors are associated with disease progression

  Correspondence to:geginat@ingm.org; lanzavecchia@ingm.org; abrignani@ingm.org; massimiliano.pagani@ifom.euBonnal RJP, Rossetti G, Lugli E, et al. Clonally expanded EOMES(+) Tr1-like cells in primary and metastatic tumors are associated with disease progression. Nat Immunol 2021;22:735-45.

  Regulatory T (Treg) cells are a barrier for tumor immunity and a target for immunotherapy. Using single-cell transcriptomics, we found that CD4+ T cells infiltrating primary and metastatic colorectal cancer and non-small-cell lung cancer are highly enriched for two subsets of comparable size and suppressor function comprising forkhead box protein P3+ Treg and eomesodermin homolog (EOMES)+ type 1 regulatory T (Tr1)-like cells also expressing granzyme K and chitinase-3-like protein 2. EOMES+ Tr1-like cells, but not Treg cells, were clonally related to effector T cells and were clonally expanded in primary and metastatic tumors, which is consistent with their proliferation and differentiation in situ. Using chitinase-3-like protein 2 as a subset signature, we found that the EOMES+ Tr1-like subset correlates with disease progression but is also associated with response to programmed cell death protein 1–targeted immunotherapy. Collectively, these findings highlight the heterogeneity of Treg cells that accumulate in primary tumors and metastases and identify a new prospective target for cancer immunotherapy.

  调节性T(Treg)细胞是肿瘤免疫的屏障,也是免疫治疗的靶点。利用单细胞转录学方法,我们发现浸润性原发和转移性结直肠癌和非小细胞肺癌的CD4+T细胞高度富集于两个具有相似大小和抑制功能的亚群:叉头盒蛋白P3+Treg和脱中胚蛋白(EOMES)+1型调节T(TR1)样细胞也表达颗粒酶K和几丁质酶-3样蛋白2。EOMES+ tr1样细胞,而不是Treg细胞,与效应T细胞的克隆相关,并在原发和转移性肿瘤中克隆扩增,这与原位增殖和分化一致。使用几丁质酶-3样蛋白2作为亚集特征,我们发现EOME+TR1样亚集与疾病进展相关,但也与程序性细胞死亡蛋白1靶向免疫治疗的应答有关。总体而言,这些发现突出了在原发肿瘤和转移瘤中聚集的Treg细胞的异质性,并确定了癌症免疫治疗的新的预期靶点。

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