Favorable prognostic impact of Natural Killer cells and T cells in high-grade serous ovarian carcinoma

Abstract

<b>Introduction:</b> The aim of the present study was to investigate the prognostic impact of intratumoral cytotoxic T cells, Natural Killer (NK) cells, neutrophils and PD-L1 expression in patients with epithelial ovarian cancer.<b>Methods:</b> All patients diagnosed with high-grade serous carcinoma (HGSC) in Denmark in 2005 were included in the study. Immunohistochemical staining for PD-L1, CD8, CD66b and CD57 was performed on tumor tissue from 283 patients. Cell densities were analyzed using a digital image analysis method. The primary endpoint was overall survival (OS).<b>Results:</b> The median OS for HGSC patients was 30 months. It was 45 months in patients with high level of CD57+ NK cells (≥10 cells/mm²) compared with 29 month in patients with low level (<10 cells/mm²) (<i>p</i> = .0310). The median OS was 37 and 25 months in patients with high vs. low level of CD8+ T cells (cutoff 80 cells/mm²) (<i>p</i> = .0008). In multivariate analysis, high numbers of CD57+ NK cells and CD8+ T cells remained independent markers of favorable OS, adjusted hazard ratio (HR) 0.67; <i>p</i> = .041, and HR 0.72; <i>p</i> = .020, respectively. PD-L1 expression was associated with improved OS (37 months vs. 22 months, <i>p</i> = .0006), but was only borderline significant in the multivariate analysis (HR 0.77, <i>p</i> = .061). CD66b + neutrophils had no association with OS.<b>Conclusions:</b> In patients with HGSC tumor-infiltrating CD57+ NK cells and CD8+ T cells had favorable prognostic impact, while PD-L1 expression had borderline favorable prognostic significance. CD66b + neutrophils had no prognostic association. These findings may influence future immunotherapy development.