Programmed death ligand-1 and CD8 tumor-infiltrating lymphocytes (TILs) as prognostic predictors in ovarian high-grade serous carcinoma (HGSC)

Abstract

Background P D-L1 is expressed in tumor cells and plays a crucial role in tumor immune escape. Tumor-infiltrating lymphocytes (TILs) as CD8 T cells contribute to reduced tumor growth. Few studies investigated the prognostic effect of PD-L1 and CD8 TILs in ovarian high-grade serous carcinoma (HGSC). In the present study, we analyzed the expression of PD-L1 and CD8 TILs in HGSC by immunohistochemistry, and results were correlated to prognosis. It was carried on 54 cases of ovarian HGSC who attended the Oncology Centre, Mansoura University, Egypt, from 2012 till 2019. Results Nearly 60% of cases showed positive PD-L1 expression in tumor cells. Regarding the clinicopathological characteristics, higher PD-L1 expression was found among patients with residual tumor (82.4%) compared to patients with no residual tumor (54.5%), with marginal statistical significance (p 0.07). PD-L1 was significantly associated with CD8 TILs expression. Higher PD-L1 expression was found among tumors with low expression of CD8 TILs with statistically significant difference (p≤0.001). Disease-free survival (DFS) was significantly lower among the group with positive expression of PD-L1 compared to the group with negative expression of PD-L1 (p 0.01), while overall survival (OS) was not associated with PD-L1 expression. On the other hand, the overall survival (OS) in patients with high CD8 expression was significantly higher than patients with low CD8 expression (p 0.043), while DFS was not significantly different among both CD8 TILS groups. Conclusions PD-L1 and CD8 TILs may become a promising therapeutic target for patients with ovarian HGSC. More studies are needed to further validate their prognostic effect. Precise identification of patients who will benefit from PD-L1 checkpoint blockade and TILs adaptive immunotherapy is mandatory.

PD-L1 Expression in Different Segments and Histological Types of Ovarian Cancer According to Lymphocytic Infiltrate

“…The presence of antitumor immune response as TILs predicts significantly better OS in EOC. Correlation between prolonged OS and the presence of TILs indicates that EOCs are for certain intrinsically immunogenic tumors [5].…”

“…PD-L1 expression in HGSC was approached in only a few studies with variable results [5]. There is a lot of contradiction about the PD-L1 expression on tumor cells concerning the type of lymphocytic infiltrate.…”

“…The analysis of PD-L1 expression with assessment TIL status could become a promising therapeutic target for patients with ovarian HGSC [5]. We need more studies to validate their therapeutic potential.…”

“…PD-L1 expressed on tumor cells interacts with PD-1 receptor on T lymphocytes and leads to inhibition of secretion cytokines and deactivation of effector T lymphocytes. Such an interaction makes tumor cells resistant to effector lymphocytes [4,5]. The PD-1/PD-L1 pathway inhibition using monoclonal antibodies has become a promising therapy in many cancers with increased survival.…”

“…Tumor-infiltrating lymphocytes (TILs) contribute to reduced tumor growth [5]. The significance of TILs and their correlation with the prognostic parameters has been the subject of many studies [7,8].…”