Immunotyping in tubo-ovarian high-grade serous carcinoma by PD-L1 and CD8+ T-lymphocytes predicts disease-free survival.

Abstract

PD-L1 immune checkpoint inhibitor expression was evaluated in high-grade serous carcinoma (HGSC) ovary in the context of the overall immune landscape to determine its prognostic value. Consecutive cases of HGSC, 50 who underwent upfront surgery followed by adjuvant chemotherapy (HGSC-U) and 50 who underwent neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (HGSC-PC) were selected. In HGSC-PC cases, the pre-NACT ascitic fluid cell blocks were included. Tumor-infiltrating lymphocytes (TILs) were scored, hotspots chosen for tissue microarray construction and immunohistochemistry performed and scored for CD4 and CD8 lymphocyte subsets, CD68+ tumor-associated macrophages (TAMs), PD-1 and PD-L1 expression. HGSC-post-chemotherapy showed increased TILs, predominantly CD8+T-lymphocytes, compared to HGSC-U. HGSC showed PD-L1 expression on tumor cells and/or TAMs in 60% cases with a linear correlation to CD4+, CD8+ TIL levels. Concordant PD-L1 expression was seen in matched pre- and post-NACT tumor cells. HGSC-PC showed higher expression of PD-L1. There was no association of PD-L1 cumulative proportion score or tumor cell score with outcome. Taking a cutoff for PD-L1 CPS at 10%, immunotype I (PD-L1+/CD-8+), corresponding to tumors with adaptive immune evasion, showed worst disease-free survival compared to all other immunotypes (p=0.03) and was more significant (p=0.01) when compared to immunotype III (PD-L1+/CD8-). Immunotyping based on PD-L1/CD8+ expression correlates to prognosis and outcome.