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

Human primary and metastatic tumors harbor CD4(+) T-reg cells that can suppress antitumor immune responses. Bonnal et al. identify an intratumoral type 1 T-reg-like CD4(+) T cell subset that expresses the transcription factor EOMES, granzyme K and CHI3L2. This EOMES+ T cell subset correlates with disease progression but is responsive to PD-1 checkpoint blockade immunotherapy. Regulatory T (T-reg) 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-reg 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-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+ 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-reg cells that accumulate in primary tumors and metastases and identify a new prospective target for cancer immunotherapy.

Automated summary

T-reg cells in tumors can suppress immune responses, but the EOMES+ Tr1-like subset shows response to PD-1 blockade immunotherapy, correlating with disease progression and therapeutic response.