GO12 : Distinct immunophenotype of tumor-infiltrating CD137+ regulatory T cells in patients with epithelial ovarian cancer

Objective: In the current study, we analyzed tumor-infiltrating regulatory T cells (TIL-Treg cells) in patients with epithelial ovarian cancer (EOC) to investigate the role of Treg cells in anti-tumor immunity of EOC. Methods: We isolated peripheral blood mononuclear cells (PBMCs) and TILs from 33 patients with newly diagnosed EOC and analyzed them using flow cytometry. First, we gated Treg cells, their fractions, and CD137+Treg cells in PBMCs and TILs. Second, we compared the expression levels of immune checkpoint receptors (ICRs) ,Treg activation molecule CD39, costimulatory molecule OX40, proliferation marker Ki-67. Furthermore, levels of Helios (marker of natural Treg cell) and chemokine receptor CCR8 were assessed to explore origin of tumor-infiltrating CD137+ Treg cells. Results: Treg cells were more enriched in TILs than PBMCs. When analyzed fraction of Treg cells, more than half of TIL-Treg cell was fraction III and few fraction I was present in TIL-Treg cells. As for fraction II (suppressive Treg cells), about 40% of TIL-Treg cells was fraction II. When comparing the fraction of peripheral Treg cell with TIL-Treg cells, the peripheral fraction II Treg cells and TIL-Treg cells showed similar expression pattern of ICRs (PD-1 and CTLA-4), CD39 and OX40. Furthermore, Helios and CCR8 were similarly high in fraction II peripheral Treg cells and TIL-Treg cells. CD137+Treg cells as antigen-specific Treg cells were also more infiltrated in TILs. CD137+Treg cells more expressed ICRs and CD39, and OX-40 than CD137-Treg cells. Among CD137+Treg cells, fraction II Treg cells was 57.3%. Most of the CD137+Treg cells were derived from natural Treg cells (Helios+CCR8+) and more proliferative than CD137-Treg cells. CD137+Treg cells showed higher expression of CTLA-4, PD-1, TIM-3, CD39, and OX40 than CD137-Treg cells. Conclusion: CD137+ TIL-Treg cells showed distinct immunosuppressive phenotype in EOC. However, further study is necessary to evaluate their suppressive function and explore clinical implication.