High expression of CD8 in the tumor microenvironment is associated with PD-1 expression and patient survival in high-grade serous ovarian cancer.

Objective: The current study assesses programmed death-1 (PD-1) receptor expression and CD3, CD4, and CD8 tumor-infiltrating lymphocytes (TILs) in high-grade serous ovarian cancer (HGSOC) and associates our results with neoadjuvant chemotherapy history and disease prognosis.

Materials and methods: We included cases diagnosed with primary HGSOC with biopsy or surgical resection materials in this study. The immunoreactivity of CD3, CD4, CD8, and PD1 was assessed immunohistochemically in tumor tissue. We analyzed TILs in two predetermined groups of high and low TIL. The relationships between clinical characteristics, PD-1, and TIL were assessed. by the χ(2) test or Fisher's Exact test. We used Kaplan-Meier survival analysis and Cox proportional hazards regression model to the connection between survival and the amounts of TIL, and PD1.

Results: Univariate analysis demonstrated that optimal debulking (p<0.001), early International Federation of Gynecology and Obstetrics stage (p=0.046), and higher scores of stromal CD8+ TIL expression (p=0.028) in tumor cells were all substantially correlated with longer disease-free survival (DFS), whereas the remaining variables analyzed, including PD-1 positivity, stromal CD3+, and CD4+ TILs, and intraepithelial CD3+, CD4+, and CD8+ TILs, were not correlated with DFS. Also, univariate analysis revealed that optimal debulking (p=0.010), and higher scores of stromal CD8+ TIL expression (p=0.021) in tumor cells were all substantially correlated with longer overall survival (OS).

Conclusion: Higher scores of stromal CD8+ TILs are substantially correlated with DFS and OS in univariate analyses, whereas scores of stromal CD3+ and CD4+ TILs, and intraepithelial CD3+, CD4+, and CD8+ TILs are not correlated with DFS and OS in both univariate and multivariate analyses. Also, we found a significant association between PD-1 positivity and the scores of stromal CD3+ TILs and intraepithelial CD8+ TILs. However, no remarkable relationship was revealed between PD-1 positivity and the survival of HGSOC cases.