Adverse prognostic impact of regulatory T-cells in testicular diffuse large B-cell lymphoma


Pollari M, et al. Eur J Haematol 2020.


OBJECTIVES: Testicular diffuse large B-cell lymphoma (T-DLBCL) is a rare and aggressive extranodal lymphoma. We have previously shown that high content of tumor-infiltrating lymphocytes (TILs) and PD-1 expressing TILs associate with better survival in T-DLBCL. In this study, we have further characterized distinct TIL subtypes and their proportions in association with patient demographics and survival.

METHODS: We used multiplex immunohistochemistry (mIHC) to characterize TIL phenotypes, including cytotoxic T-cells (CTLs) (CD8⁺, OX40⁺, Granzyme B⁺, Ki-67+ , LAG-3⁺, TIM-3⁺, PD-1⁺), CD4+ T-cells (CD3+ , CD4+ , TIM-3+ , LAG-3+ ), regulatory T-cells (Tregs; CD3+ , CD4+ , FoxP3+ ), and T helper 1 cells (Th1; CD3+ , CD4+ , T-bet+ ) in 79 T-DLBCLs, and correlated the findings with patient demographics and outcome.

RESULTS: We observed a substantial variation in TIL phenotypes between the patients. The most prominent CD8+ TILs were Ki-67+ and TIM-3+ CTLs, whereas the most prominent CD4+ TILs were FoxP3⁺ Tregs. Despite the overall favorable prognostic impact of high TIL content, we found a subpopulation of T-bet⁺FoxP3+ Tregs that had a significant adverse impact on survival. Lower content of CTLs with activated or exhausted phenotypes correlated with aggressive clinical features.

CONCLUSIONS: Our results demonstrate significant variation in TIL phenotypes and emphasize the adverse prognostic impact of Tregs in T-DLBCL.