Istituto Nazionale Genetica Molecolare Romeo ed Enrica Invernizzi, Milan, Italy.
FIRC Institute of Molecular Oncology (IFOM), Milan, Italy.
Nat Immunol. 2021 Jun;22(6):735-745. doi: 10.1038/s41590-021-00930-4. Epub 2021 May 20.
Regulatory T (T) 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 T 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 T 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 T cells that accumulate in primary tumors and metastases and identify a new prospective target for cancer immunotherapy.
调节性 T（T）细胞是肿瘤免疫的障碍，也是免疫疗法的靶点。我们通过单细胞转录组学发现，浸润原发性和转移性结直肠癌和非小细胞肺癌的 CD4 T 细胞高度富含两个大小相当且具有抑制功能的亚群，包括叉头框蛋白 P3 T 和同源物（EOMES）类型 1 调节性 T（Tr1）样细胞，也表达颗粒酶 K 和几丁质酶 3 样蛋白 2。EOMES Tr1 样细胞而非 T 细胞与效应 T 细胞具有克隆相关性，并在原发性和转移性肿瘤中克隆扩增，这与其在原位的增殖和分化一致。使用几丁质酶 3 样蛋白 2 作为亚群标志，我们发现 EOMES Tr1 样亚群与疾病进展相关，但也与程序性细胞死亡蛋白 1 靶向免疫治疗的反应相关。总之，这些发现强调了在原发性肿瘤和转移灶中积累的 T 细胞的异质性，并确定了癌症免疫治疗的一个新的有前景的靶点。
