FoxP3+ Regulatory T-Cell Quantities in Nodal T-Follicular Helper Cell Lymphomas and Peripheral T-Cell Lymphomas Not Otherwise Specified and Their Impact on Overall Survival

Cancers (Basel). 2024 Nov 29;16(23):4011. doi: 10.3390/cancers16234011.

Abstract

Background/objectives: The tumour microenvironment (TME) plays an important role in the development and progression of cancer and it differs among lymphomas, both with respect to the composition and quantity of specific tumour-infiltrating immune cells (TICs), such as FoxP3+ regulatory T cells (Tregs). The role of FoxP3+ Tregs in the TME of peripheral T-cell lymphomas (PTCLs) is complex, and their impact on overall survival (OS) remains unclear. Consequently, we aim to evaluate and compare the FoxP3+ cell quantity in nodal PTCLs and reactive lymph nodes (LNs), with a focus on investigating their impact on OS.

Methods: excisional lymph node (LN) biopsies from 105 nodal PTCLs and 17 reactive LNs are immunohistochemically stained for FoxP3. Visual scoring of FoxP3+ cells is performed, and different cut-off values are used to evaluate the impact of FoxP3+ cell quantity on OS.

Results: FoxP3+ cells are present in the TME of all cases, except for four cases where FoxP3+ is expressed in lymphoma cells. Lower FoxP3+ cell quantities are observed in certain nodal PTCL subtypes compared to reactive LNs. Patients with high FoxP3+ cell quantities show improved OS. However, the FoxP3+ cell quantity is not confirmed as an independent prognostic biomarker.

Conclusions: these findings underscore the promise of FoxP3+ cell quantities as added value in prognosis and highlight the potential benefits of Treg-stimulating therapies in PTCLs.

Keywords: FoxP3+; cut-off value; overall survival; peripheral T-cell lymphoma; prognostic biomarker; regulatory T cells.