Gallego, AlejandroMendiola, MartaHernando, BarbaraBerjon, AlbertoCadiz, AliceChaves-Urbano, BlasHeredia-Soto, VictoriaSpagnolo, EmanuelaHernández Gutiérrez, AliciaHardisson, DavidMacintyre, GeoffRedondo, AndresGarcia, Maria Jose2025-03-202025-03-202022-08-01Int J Gynecol Cancer . 2022 Aug 1;32(8):1009-1016https://hdl.handle.net/20.500.12105/26528This research received funding from the 7th Jan Vermorken Research Grant for Research in Gynaecological Cancer awarded by the Spanish Group for Investigation on Ovarian Cancer (GEICO). This study was funded by the Accion Estrategica en Salud (AES) from the Instituto de Salud Carlos III (PI19/01730) and co--funded by the European Regional Development Fund (FEDER). BH, GM and MJG were supported by funding from the Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Science and Innovation.Cancer-related systemic inflammation has been associated with prognosis in multiple cancer types. Conversely, local inflammation, which is characterized by dense intratumoral immune infiltrates, is a favorable predictor of survival outcome. However, these survival associations are not well established in ovarian cancer, particularly in the less frequent endometrioid and clear cell endometriosis associated histotypes.This retrospective study included 119 patients (63 endometrioid and 56 clear cell ovarian carcinomas). We performed a comprehensive survival association analysis of both systemic (neutrophil-to-lymphocyte ratio or presence of endometriosis) and local inflammation markers (CD3+ and CD8+ tumor infiltrating lymphocytes) using multivariate Cox proportional hazards models that account for confounding factors.Medium to high levels of intraepithelial CD8+ tumor infiltrating lymphocytes are associated with longer survival in endometrioid ovarian cancer (p=0.04). In addition, we found that intraepithelial CD8+ tumor infiltrating lymphocytes are prognostic in clear cell ovarian cancer (p=0.02), and that intraepithelial CD3+ tumor infiltrating lymphocytes are also associated with improved outcome (p=0.02). Furthermore, intratumoral CD3+ and CD8+ tumor infiltrating lymphocytes showed improved prognosis in the endometrioid subtype (p<0.1). No prognostic value was observed for systemic immune markers.In this study, patients with endometrioid and clear cell ovarian cancer with moderate to high CD8+ and CD3+ intraepithelial tumor infiltrating lymphocytes had longer overall survival. Higher expression of intratumoral CD3+ and CD8+ tumor infiltrating lymphocytes also showed an improved outcome in endometrioid ovarian cancer. In contrast, systemic inflammation, evaluated by neutrophil-to-lymphocyte ratio or presence of endometriosis, did not have a prognostic impact in these histologic subtypes.engVoRhttp://creativecommons.org/licenses/by-nc-nd/4.0/ovarian cancerAttribution-NonCommercial-NoDerivatives 4.0 International354372723281009-1016INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCERopen access