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

Raoul Jean Pierre BonnalGrazisa RossettiEnrico LugliMarco De SimonePaola GruarinJolanda BrummelmanLorenzo DrufucaMarco PassaroRamona BasonFederica GervasoniGiulia Della ChiaraClaudia D'OriaMartina MartinovicSerena CurtiValeria RanzaniChiara CordiglieriGiorgia AlvisiEmilia Maria Cristina MazzaStefania OlivetoYlenia SilvestriElena CarelliSaveria MazzaraRoberto BosottiMaria Lucia SarnicolaChiara GodanoValeria BevilacquaMariangela LorenzoSalvatore SienaEmanuela BonoldiAndrea Sartore-BianchiAlessio AmatuGiulia VeronesiPierluigi NovellisMarco AlloisioAlessandro GianiNicola ZucchiniEnrico OpocherAndrea Pisani CerettiNicolò Maria MarianiStefano BiffoDaniele PratiAlberto BardelliJens GeginatAntonio LanzavecchiaSergio AbrignaniMassimiliano Pagani
Published in: Nature immunology (2021)
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.
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