High levels of Tim-3+Foxp3+Treg cells in the tumor microenvironment is a prognostic indicator of poor survival of diffuse large B cell lymphoma patients

Foxp3+Treg cells display phenotypic and functional heterogeneity, which express high levels of T cell immunoglobulin and mucin-domain containing-3 (Tim-3) in the tumor microenvironment (TME) of colorectal and lung cancer. High abundance of Tim-3+Foxp3+Treg (TFT) cells are associated with poor prognosis in these patients. However, the expression patterns and roles of TFT cells in TME of diffuse large B cell lymphoma (DLBCL) remain to be established. Double immunofluorescence and flow cytometry analyses were employed to investigate TFT cell enrichment in paraffin-embedded fresh tumor tissues from patients with DLBCL. Spearman's or Pearson's correlation and Kaplan-Meier survival analyses were further applied to decide the prognostic value of TFT cell levels in DLBCL. The IL-10-secreting function of TFT cells in vitro was examined via flow cytometry and ELISA. Our results showed for the first time that TFT cells are highly enriched in TME of DLBCL patients and associated with predictions of poor prognoses. TFT cell-induced secretion of IL-10 in the TME was suppressed by an anti-Tim-3 antibody in vitro. In conclusion, high abundance of TFT cells in the TME is predictive of poor outcomes of DLBCL. TFT cells promote DLBCL development partly by secreting IL-10 in the TME. Anti-Tim-3 antibodies (that block IL-10 secretion) may present an effective therapeutic agent for DLBCL.