253P - Anti-PD-1-induced reinvigoration of tumour-infiltrating CD8+ T cells in epithelial ovarian cancer patients is correlated with T cell factor-1

Background

Epithelial ovarian cancer (EOC) is an aggressive gynecologic malignancy with poor prognosis. Recently, immune checkpoint inhibitors (ICIs) had remarkable success in various malignancies. However, clinical trials of anti-PD-1 with ovarian cancer patients have failed to show clinical benefits. Several factors may limit the efficacy of ICIs, including the exhaustion status of tumor-infiltrating lymphocytes (TILs). In this study, we examined the immuno-phenotypes and ICI-induced reinvigoration of CD8⁺ TILs from EOC patients to understand the nature of T-cell exhaustion in EOC.

Methods

We isolated peripheral blood mononuclear cells (PBMCs) and TILs from 29 EOC patients and examined the immuno-phenotypes using flow cytometry. Furthermore, to investigate the pattern of ICIs-induced reinvigoration of CD8⁺ TILs, we ex vivo stimulated TILs with anti-CD3 in the presence of ICIs and assessed their proliferation.

Results

CD8⁺ TILs had significantly increased expression of immune checkpoint receptors, including PD-1, CTLA-4, and Tim-3 compared to peripheral blood CD8⁺ T cells. Furthermore, the frequency of T cell factor-1⁺ (TCF-1, a transcription factor involved in T cell stemness) CD8⁺ T cells was decreased in TILs than PBMCs. Among CD8⁺ TILs, CTLA-4, and Tim-3 tended to be more expressed on PD-1⁺ cells than PD-1^- cells. However, compared with PD-1^-CD8⁺ TILs, PD-1⁺CD8⁺ TILs exhibited significantly low expression of TCF-1. When we evaluated the proliferation of CD8⁺ TILs after ex vivo stimulation with anti-CD3 and ICIs, we found that anti-PD-1 could reinvigorate CD8⁺ TILs and reinvigorating response was correlated with the frequency of TCF-1⁺ cells among PD-1⁺CD8⁺ TILs.

Conclusions

We conclude that TCF-1 could determine the anti-PD-1-induced reinvigoration of CD8⁺ TILs in EOC patients. The present study has significance in that it may provide the rationale and directions for future translational research to predict and optimize ICI-induced response in EOC patients.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

All authors have declared no conflicts of interest.