Unique immune characteristics and differential anti-PD-1-mediated reinvigoration potential of CD8 TILs based on mutation status in epithelial ovarian cancers.

BACKGROUND

We aimed to investigate the distinct immunological characteristics of the tumor immune microenvironment in epithelial ovarian cancer (EOC) according to mutations status and differential PD-1 expression levels.

METHODS

Tumor-infiltrating lymphocytes (TILs) were collected from patients with newly diagnosed advanced-stage EOC (YUHS cohort, n=117). This YUHS cohort was compared with The Cancer Genome Atlas (TCGA) data for ovarian serous cystadenocarcinoma (n=482), in terms of survival outcomes and immune-related gene profiles according to status. We used multicolor flow cytometry to characterize the immune phenotypes and heterogeneity of TILs with or without mutations. functional assays were conducted to evaluate the reinvigorating ability of CD8 TILs on anti-PD-1 treatment.

RESULTS

We found that EOC patients with mutations (mt) exhibited better survival outcomes and significantly higher tumor mutation burden (TMB), compared with non-mutated (wt) patients. Furthermore, CD8 TILs within mt tumors displayed characteristics indicating more severe T-cell exhaustion than their wt counterparts. Notably, the capacity for anti-PD-1-mediated reinvigoration of CD8 TILs was significantly greater in wt tumors compared with mt tumors. Additionally, within the wt group, the frequency of PD-1CD8 TILs was positively correlated with the reinvigoration capacity of CD8 TILs after anti-PD-1 treatment.

CONCLUSION

Our results highlight unique immune features of CD8 TILs in EOC and a differential response to anti-PD-1 treatment, contingent on mutation status. These findings suggest that immune checkpoint blockade may be a promising frontline therapeutic option for selected wt EOC patients.