Search

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.

Differences in the gene mutation spectra of younger and older Chinese adult AML patients and the prognostic significance of these differentially presented gene mutations are rarely reported. One hundred and thirteen newly diagnosed Chinese adults with AML, divided into groups of younger and older patients, were enrolled in this study. Bone marrow samples from the patients were analyzed using targeted next-generation sequencing with a panel of 141 genes. Ninety-eight mutated genes were detected and the top 10 mutated genes were KMT2D, FLT3, FAT1, ASXL1, NRAS, DNMT3A, RELN, TET2, JAK2, and KRAS. The top five functional groups were the tyrosine kinase pathway, transcription factors, DNA methylation, chromatin modifiers, and the JAK-STAT signaling pathway. Younger patients exhibited higher incidences of KMT2D (33.8% vs 10.4%, P = 0.004) and KRAS (15.4% vs 2.1%, P = 0.042) mutations than older patients; whereas, older patients harbored more SRSF2 (20.8% vs 0%, P = 0.002), transcription factor (85.4% vs 67.7%, P = 0.031), DNA methylation (58.3% vs 36.9%, P = 0.024), and RNA splicing (31.3% vs 12.3%, P = 0.013) mutations than younger patients. Moreover, patients with SRSF2 mutations exhibited a lower rate of overall survival (P 0.001) and relapse-free survival (P 0.001) than patients carrying wild-type SRSF2. In conclusion, rarely reported KMT2D, FAT1, and RELN mutations were detected at high frequencies in our cohort. The gene mutation spectrum of older patients was different to that of younger patients. Moreover, older patients harbored more SRSF2 mutations, which predicted lower rates of overall and relapse-free survival.