Combined PD-1/PD-L1 and tumor-infiltrating immune cells redefined a unique molecular subtype of high-grade serous ovarian carcinoma

Abstract

Background High-grade serous ovarian carcinoma is highly heterogeneous, and although many studies have been conducted to identify high-grade serous ovarian carcinoma molecular subtypes that are sensitive to immunotherapy, no precise molecular subtype has been proposed to date. Immune cell infiltration and immune checkpoints are highly correlated with immunotherapy. Here, we investigated immune cell infiltration and immune checkpoint values for prognosis and precise immunotherapy for high-grade serous ovarian carcinoma based on molecular subtype classification. Results “High antigen-presenting cells infiltration molecular subtype of high-grade serous ovarian carcinoma” was identified in immune cell infiltration profiles. Each of the three immune cell infiltration clusters (A, B, and C) demonstrated distinct immune cell characterization, with immune cell infiltration cluster C exhibiting high antigen-presenting cell infiltration, improved prognosis, and higher sensitivity to immunotherapy. Programmed death-1/programmed death ligand 1 has a prognostic and predictive role that can help classify molecular subtypes. Conclusions Our findings redefined a unique molecular subtype of high-grade serous ovarian carcinoma, suggesting that high-grade serous ovarian carcinoma patients with higher antigen-presenting cell infiltration and programmed death-1/programmed death ligand 1 expression can benefit from precise immunotherapy.

The Prognostic Significance of Tumor-Infiltrating Lymphocytes, PD-L1, BRCA Mutation Status and Tumor Mutational Burden in Early-Stage High-Grade Serous Ovarian Carcinoma—A Study by the Spanish Group for Ovarian Cancer Research (GEICO)

“…We observed that only 8% of early-stage HGSOC in this series expressed PD-L1 in tumor cells and that this expression was not associated with prognosis. Series that analyzed PD-L1 in HGSOC are heterogeneous in terms of clinicopathological features, staining assays, cut-off values and the evaluation of tumor cells, inflammatory cells or both [ 28 , 29 , 30 , 31 , 32 , 33 , 34 ]. In previous studies, the percentage of positive tumor cells ranged from 24% [ 28 ] to 88% [ 29 ].…”

Prognostic Significance of Programmed Cell Death Ligand 1 Expression in High-Grade Serous Ovarian Carcinoma: A Systematic Review and Meta-Analysis

“…They have contemplated innate confounding factors within the IHC study methods as potential reasons for these disparities [12][13][14]16,24,25]. However, even studies utilizing mRNA expression data have shown similar contradictions in the prognostic significance of PD-L1 expression in HGSOC [14,24,48]. Furthermore, Wieser et al were unable to find a correlation between PD-L1 IHC data and mRNA data, suggesting the need for a more accurate and standardized method for IHC evaluation [49].…”

Recent Insight about HE4 Role in Ovarian Cancer Oncogenesis

“…Additionally, some recent studies have shown that HE4 is involved in promoting ovarian tumor immune evasion, through influencing expression of two proteins, osteopontin (OPN) and dual specificity phosphatase 6 (DUSP6): consequently, through targeting of HE4, it may be possible to downregulate molecular mechanisms that promote tumorigenesis and to restore a normal tumor immune response too [ 85 ].…”