Clinical significance of tumor infiltrating lymphocytes in high-grade serous ovarian carcinoma

Abstract

Objective: To compare intratumoral tumor-infiltrating lymphocytes (TIL) in a cohort of high-grade serous ovarian carcinoma patients between those who treated with neoadjuvant chemotherapy (NACT) and primary debulking surgery (PDS), and to determine the clinical and prognostic significance of TIL in high-grade serous ovarian carcinoma. Methods: Tissue microarrays and immunohistochemistry were used to assess the quantity of CD3+, CD4+ and CD8+ lymphocytes in tumor tissue from 138 high-grade serous ovarian carcinoma (PDS n=84, NACT n=54) which were collected from January 2013 to January 2016 at West China Second University Hospital, Sichuan University. TIL was analysed in two predefined groups of low and high TIL. The associations between clinical features and TIL were evaluated by χ(2) test or Fisher's exact test, and Kaplan-Meier survival analysis and Cox proportional hazards regression model were used for the association between the amounts of TIL and progression free survival. Results: There was no difference in TIL/HPF (high-power field) counting in tumor tissue between PDS and NACT (P>0.05), and in the PDS cohort, CD3+, CD4+ and CD8+TIL were not associated with any clinical features like age, FIGO stage, tumor size and chemotherapy sensitivity, however, in the NACT cohort, CD8+TIL was strongly associated with chemotherapy sensitivity. The univariable analysis supported that high CD8+TIL in tumor tissue was associated with longer progression free survival both in the PDS and NACT cohort(P=0.030, P=0.032), but not CD4+TIL, in the NACT cohort, high CD3+TIL were also associated with longer progression free survival (P=0.019). Finally, in multivariate analysis, only the high CD8+TIL had prognostic significance (HR=0.369, 95%CI=0.176-0.772, P=0.008). Conclusion: High CD8+lymphocytes density in tumor tissue was significantly associated with improved progression free survival in high-grade serous ovarian carcinoma. Besides, the CD8+lymphocytes density could be served as a potential marker of the chemotherapy sensitivity in patients who treated with neoadjuvant chemotherapy.