CD39+ and Tim3+ T reg are potential effector cells in the peripheral blood and tumor microenvironment of head and neck squamous cell carcinoma patients

Introduction Regulatory T cells (T _reg) constitute an immunosuppressive, tumor-promoting cell population in the head and neck tumor microenvironment. However, T _reg  are phenotypically and functionally heterogeneous and can be subdivided into naive (nT _reg, CD45RA+FoxP3low), effector (eT _reg, CD45RA−FoxP3high) and non-suppressive (nsT _reg, CD45RA−FOXP3low) subpopulations. Here we investigate the role of eT _reg  in head and neck squamous cell carcinoma (HNSCC).

Methods Peripheral blood from 50 head and neck squamous cell carcinoma patients was analyzed by multiparameter FACS (CD8, CD4, CD45RA, FoxP3, Neuropilin-1, CD39, PD-1, Tim-3, LAG-3, CTLA-4, TIGIT, CD69, pAKT, Ki67, Bcl2) and cytokine staining after stimulation (IFNγ, TNFα). Immune cells, particularly T _reg, from peripheral blood and tumor microenvironment of 18 HNSCC patients were analyzed by single cell RNA sequencing.

Results eT _reg  express a higher percentage of checkpoint receptors (PD-1, Tim-3, CTLA-4, CD39) compared to naive and non-suppressive regulatory T cells. In addition, eT _reg  show higher Ki67 expression, which correlates with fewer apoptosis signaling pathways (pAKT, Bcl2) and higher FoxP3 expression. Single cell RNA sequencing can also detect an eT _reg cell population (CD39+, Tim3+) intratumorally.

Summary Regulatory T cells are a heterogeneous cell type with subpopulations that differ phenotypically and functionally. Future studies should take into account the effect of the divers subpopulation, especially eT _reg, on survival and treatment response of HNSCC patients.

Publication History

Article published online:
12 May 2023