Impact of PD-L1 and T-cell inflamed gene expression profile on survival in advanced ovarian cancer

Abstract

<jats:sec><jats:title>Objective</jats:title><jats:p>Programmed death ligand 1 (PD-L1) expression affects tumor evasion of immune surveillance. The prognostic value and relationship of PD-L1 expression to T-cell–inflamed immune signatures in ovarian cancer are unclear. The purpose of this study is to evaluate the impact of PD-L1 on overall survival and its correlation with an immune-mediated gene expression profile in patients with advanced ovarian cancer.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>PD-L1 expression in tumor and immune cells was assessed by immunohistochemistry, and PD-L1–positive expression was defined as a combined positive score ≥1; a T-cell–inflamed gene expression profile containing interferon γ response genes was evaluated using extracted RNA from surgical samples. Associations between PD-L1 expression, gene expression profile status, and overall survival were analyzed using the Kaplan-Meier method, log-rank test, and multivariate Cox proportional hazards regression models.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>A total of 376 patients with advanced epithelial ovarian, primary peritoneal, or fallopian tube cancer treated by cytoreductive surgery and platinum-based therapy were included. PD-L1–positive expression was observed in 50.5% of patients and associated with more advanced stage (p=0.047), more aggressive histologic subtype (p=0.001), and platinum sensitivity defined by increasing treatment-free interval from first platinum-based chemotherapy to next systemic treatment (p=0.027). PD-L1–positive expression was associated with longer overall survival in multivariate analyses (adjusted HR 0.72, 95% CI 0.56 to 0.93). In subgroup analyses, this association was most pronounced in patients with partially platinum-sensitive disease (treatment-free interval ≥6 to &lt;12 months). T-cell–inflamed gene expression profile status correlated with PD-L1 expression (Spearman, <jats:italic>ρ</jats:italic>=0.712) but was not an independent predictor of overall survival.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>PD-L1 expression is associated with longer overall survival among advanced ovarian cancer patients. PD-L1 expression may be an independent prognostic biomarker.</jats:p></jats:sec>

Lynch syndrome-associated epithelial ovarian cancer and its immunological profile

“…The expression was reported by the combined positive score (CPS) defined as the number of PD-L1 staining cells (viable tumor cells, and lymphocytes and macrophages within tumor nests or next to it) divided by viable tumor cells x 100. PD-L1 expression was defined as CPS ≥1 [20,21]. PD-L1 expression was scored by two independent observers (MR and CT) and discussed whenever there was discordance.…”

Immunology and Immune Checkpoint Inhibition in Ovarian Cancer – Current Aspects

“…PD-L1 expression was initially studied mostly in tumour cells. In particular, while previous reports showed a significant correlation of PD-L1 tumour cell expression with poor survival 28 , 97 , 99 , other groups demonstrated just the opposite, correlating PD-L1 with improved immune infiltration and prolonged survival 100 , 101 , 102 , 103 , 104 . This may be explained by a general increase in IFN-γ response in these tumours as IFN-γ on the one hand delivers an effective anti-tumour response, on the other hand it is a very potent inducer of PD-L1 expression in ovarian cancer cells 97 , 100 .…”

“…Die PD-L1-Expression wurde zunächst vor allem auf den Tumorzellen untersucht. Während insbesondere frühere Berichte eine signifikante Korrelation der PD-L1-Tumorzellexpresion mit einem schlechten Überleben zeigten 28 , 97 , 99 , zeigen andere Arbeitsgruppen genau das Gegenteil, und korrelieren PD-L1 mit einer verbesserten Immuninfiltration und einem verlängerten Überleben 100 , 101 , 102 , 103 , 104 . Dies mag sich durch eine generell gesteigerte IFN-γ-Antwort in diesen Tumoren erklären, denn IFN-γ sorgt einerseits für eine effektive Anti-Tumor-Antwort im Ovarialkarzinom, andererseits ist es ein sehr potenter Induktor einer PD-L1-Expression in Ovarialkarzinomzellen 97 , 100 .…”

PD-L1 Expression on Circulating Tumour-Derived Microvesicles as a Complementary Tool for Stratification of High-Grade Serous Ovarian Cancer Patients

“…In analogy with earlier studies in different tumour settings [40,41], future studies aimed at optimising OC patient stratification for anti-PD-1/anti-PD-L1 treatments might benefit from measuring circulating TC-derived PD-L1 + MVs. Noteworthily, complementing PD-L1 assessment by IHC with quantification of plasma levels of PD-L1 + TC-derived MVs might also contribute to solve the still controversial issue of the prognostic significance of PD-L1 expression on TCs in OC patients-either high expression indicating poor prognosis [42,43], favourable prognosis [10,44,45], or irrelevancy [37,38].…”

“…This immunotherapeutic approach requires that tumour cells and/or tumour-infiltrating immune cells express PD-L1. Despite the fact that ≥50% of advanced stage OCs express PD-L1 [10], data from clinical trials have shown unsatisfactory response rates [11][12][13][14][15][16]. Nevertheless, other trials have been designed and are currently ongoing (e.g., the ENGOT-ov46/AGO/DUO-O, ENGOT-OV43/KEYLYNK-001, and ATHENA phase III clinical studies).…”