학술논문
Clonally expanded EOMES.sup.+ Tr1-like cells in primary and metastatic tumors are associated with disease progression
eomesodermin homolog
eomesodermin homolog
Document Type
Report
Author
Bonnal, Raoul J. P.; Rossetti, Grazisa; Lugli, Enrico; De Simone, Marco; Gruarin, Paola; Brummelman, Jolanda; Drufuca, Lorenzo; Passaro, Marco; Bason, Ramona; Gervasoni, Federica; Cordiglieri, Chiara; D'Oria, Claudia; Martinovic, Martina; Curti, Serena; Ranzani, Valeria; Alvisi, Giorgia; Chiara, Giulia Della
Source
Nature Immunology. June 2021, Vol. 22 Issue 6, p735, 11 p.
Subject
Language
English
ISSN
1529-2908
Abstract
Author(s): Raoul J. P. Bonnal [sup.1] [sup.2] , Grazisa Rossetti [sup.1] [sup.2] , Enrico Lugli [sup.3] [sup.4] , Marco De Simone [sup.1] [sup.23] , Paola Gruarin [sup.1] , Jolanda Brummelman [...]
Regulatory T (T.sub.reg) cells are a barrier for tumor immunity and a target for immunotherapy. Using single-cell transcriptomics, we found that CD4.sup.+ 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.sup.+ T.sub.reg and eomesodermin homolog (EOMES).sup.+ type 1 regulatory T (Tr1)-like cells also expressing granzyme K and chitinase-3-like protein 2. EOMES.sup.+ Tr1-like cells, but not T.sub.reg 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.sup.+ 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.sub.reg cells that accumulate in primary tumors and metastases and identify a new prospective target for cancer immunotherapy. Human primary and metastatic tumors harbor CD4.sup.+ T.sub.reg cells that can suppress antitumor immune responses. Bonnal et al. identify an intratumoral type 1 T.sub.reg-like CD4.sup.+ T cell subset that expresses the transcription factor EOMES, granzyme K and CHI3L2. This EOMES.sup.+ T cell subset correlates with disease progression but is responsive to PD-1 checkpoint blockade immunotherapy.
Regulatory T (T.sub.reg) cells are a barrier for tumor immunity and a target for immunotherapy. Using single-cell transcriptomics, we found that CD4.sup.+ 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.sup.+ T.sub.reg and eomesodermin homolog (EOMES).sup.+ type 1 regulatory T (Tr1)-like cells also expressing granzyme K and chitinase-3-like protein 2. EOMES.sup.+ Tr1-like cells, but not T.sub.reg 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.sup.+ 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.sub.reg cells that accumulate in primary tumors and metastases and identify a new prospective target for cancer immunotherapy. Human primary and metastatic tumors harbor CD4.sup.+ T.sub.reg cells that can suppress antitumor immune responses. Bonnal et al. identify an intratumoral type 1 T.sub.reg-like CD4.sup.+ T cell subset that expresses the transcription factor EOMES, granzyme K and CHI3L2. This EOMES.sup.+ T cell subset correlates with disease progression but is responsive to PD-1 checkpoint blockade immunotherapy.