Background: Tim-3 is emerging as a promising target for antitumor immunotherapy. A number of clinical trials are ongoing to evaluate anti-Tim-3 therapies as a single agent or combinations in solid tumors and hematologic malignancies. However, there remains a considerable lack of data related to the information of Tim-3 signaling in diffuse large B-cell lymphoma (DLBCL), especially the genetic characteristics and immune microenvironment. Methods: Here, next-generation sequencing was utilized to identify DLBCLs harboring genetic mutations of Tim-3 ligand, and multiple immunofluorescence staining and quantitative pathological analysis techniques were applied to determine the immune microenvironment. Results: Three genetic mutations of galectin-9, which is a major ligand of Tim-3, were identified in six DLBCL patients (6/188, 3.2%). And these mutations had never been reported in DLBCL according to the COSMIC database. We further found that the Tim-3 mRNA level was significantly higher in DLBCL compared to that of normal B cells through the Oncomine database. Using multiplexed immunofluorescence staining, we found that patients with Tim-3 expression on tumor-infiltrating lymphocytes (Tim-3 + TILs) experienced significantly poorer outcomes than those with Tim-3-TILs (p ¼ 0.041), and the median survival times were 65.0 months (95% CI: 71.2e88.6) and 79.9 months (95% CI: 54.4e75.6), respectively. Furthermore, we defined a novel subtype of exhausted T cells, named as exhausted Tim-3 + CD8 + T cells, and also found that patients with exhausted Tim-3 + CD8 + T cells (median survival, 62.8 months, 95% CI: 50.0e75.6) had a significantly shorter survival than those with non-exhausted Tim-3-CD8 + T cells (median survival, 82.5 months, 95% CI: 72.0e92.9) (p ¼ 0.034). Conclusions: Overall, our findings provid an important addition to the genetic information of Tim-3 ligand in DLBCL. And we uncovered that patients with Tim-3 + TILs and exhausted Tim-3 + CD8 + T cells exhibited inferior survival, supporting potential strategies to block Tim-3 alone or in combination with other immune checkpoints as treatment options for DLBCL patients.
with a worse OS. The high CNS relapse rate suggests that patients with high grade PPL should receive CNS directed prophylaxis. Introduction: Waldeyer's ring (WR) consists of lymphoid tissue located in the pharyngeal and tubal tonsils, which are at the pharynx to the back of the oral cavity and the base of the tongue, as well as in the palatine and lingual tonsils. Diffuse large B-cell lymphoma of Waldeyer's ring (WR-DLBCL) is an extremely rare malignancy, and radiotherapy (RT) can improve survival for early-stage WR-DLBCL patients. However, the superiority of sequential chemotherapy/radiotherapy (CT+RT) and sandwich therapy (ST) remains unclear. Methods: Eighty-two primary early-stage WR-DLBCL patients treated with CT+RT, ST or chemotherapy (CT) alone were enrolled. Treatment response and patient survival were evaluated. The clinicopathological parameters impacting PFS or OS were analysed by univariate analyses. The Kaplan-Meier test was used to analyse survival.456 ABSTRACT Independent prognostic factors for PFS and OS were further studied using multivariate analyses. Results: The ORR of patients treated with CT+RT and ST were 100% and 95.2% respectively, which were higher than the ORR of patients treated with CT alone (100% vs 90.3% and 95.2% vs 90.3%). Complete response of patients treated with CT+RT tended to be better than that of patients treated with ST (70.0% vs 61.9%). Importantly, patients treated with CT+RT could maintain the higher CR rate than those treated with ST (73% vs 33.3%) and those treated with CT alone (73% vs 45.2%) during the long follow-up. Patients treated with CT+RT but not ST had significantly superior OS (P=0.003) to the survival of patients treated with CT alone. Patients treated with CT+RT experienced better outcomes than those treated with ST did (5-year PFS, 47.4% vs 23.8%, P=0.049; 5-year OS, 83.3% vs 50.0%, P=0.032).The univariate analysis showed that CT+RT treatment regimen was significantly associated with better survival.Conclusions: CT+RT was superior to ST and improved the survival for primary early-stage WR-DLBCL patients.
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