By analyzing CD4+ T cells from CRC and NSCLC primary tumors and metastases, Bonnal
et al. showed intratumoral enrichment of clonotypically distinct Foxp3+ Treg cells and Eomes+granzyme K+ Foxp3- type 1 regulatory T (Tr1)-like cells. Both subsets were also shown in melanoma, breast, and liver tumors. Tr1-like cells expressed PD-1 and chitinase-3-like protein 2 (CHI3L2) as markers, produced IL-10 and IFNγ, suppressed CD4+ and CD8+ T cell proliferation comparably to Foxp3+ Tregs, and were increased in more advanced disease. High CHI3L2 expression correlated with good response to anti-PD-1/PD-L1 therapy in patients with melanoma.
Contributed by Paula Hochman
ABSTRACT: 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.