Abstract 6485: Prognostic impact of immune cells in vulvar carcinomas
Authors: Zhihao Huang, Elena Bady, Maximilian Lennartz, Lisa Hornsteiner, Jan Hendrik Müller, Monika Kaszubowski, Ronald Simon, Guido Sauter, Sven Mahner, Niclas Blessin, Nikolaus de Gregorio, Rüdiger Klapdor, Matthias Kalder, Elena I Braicu, Sophie Fürst, Maximilian Klar, Hans-Georg Strauß, Katharina Prieske, Linn Wölber
Journal: Cancer Research (2025)

Abstract Quantification of tumor infiltrating lymphocytes (TILs) and immune checkpoints in the cancer microenvironment has become of increasing interested in immuno-oncology. Vulvar cancer is emerging as a promising target for immune checkpoint blockade therapy. However, only little is known about the presence of TILs and the expression of immune checkpoint molecules in the tumor microenvironment and its predictive value in vulvar cancer. To better comprehend the role of immune cell expression and composition in vulvar cancer, a tissue microarray containing 479 vulvar cancer samples with clinic-pathological data was analyzed by multiplex fluorescence immunohistochemistry including 21 marker proteins to determine the composition of the immune cell infiltrate. Benjamini-Hochberg correction for multiple testing was applied. A total of 479 (85, 4%) of the 561 cancers had interpretable results for all 21 markers. The identified immune cell types included cytotoxic-, T-helper- and regulatory T-cells, M1/M2 macrophages, dendritic cells, B-cells, TIM-3, PD-1 and CTLA-4 on immune cells and PD-L1 on immune and tumor cells. Comparison with clinical data revealed significant associations between prolonged progression-free survival and low expression of PD-1 (p=0.008) and TIM3 (p=0.039) on CD8+ T-cells, as well as low PD-L1 expression on M1 macrophages (p=0.046), dendritic cells (p=0.028), and tumor cells (p=0.013). Comparison with the human papilloma virus (HPV) status of the cancers showed a link between high numbers of tumor infiltrating B-cells and a favorable overall survival in HPV+ vulvar carcinomas (p=0.0464, AUC:0.67), but not in the HPV-negative subgroup. The quantification of immune cells alone did not reveal any significant correlation between the overall extent of inflammation and the histopathological parameters of the aggressive disease or the patient outcome. These data suggest that the impact of the immune reaction on the prognosis of vulvar carcinoma patients may be less dramatic than seen for other tumors. However, major differences of the role of anti-tumor immunogenicity between HPV positive and negative cancers, as well as a particular prognostic role of the quantity of B-lymphocytes and the expression of multiple checkpoint proteins is highlighted. Citation Format: Zhihao Huang, Elena Bady, Maximilian Lennartz, Lisa Hornsteiner, Jan Hendrik Müller, Monika Kaszubowski, Ronald Simon, Guido Sauter, Sven Mahner, Niclas Blessin, Nikolaus de Gregorio, Rüdiger Klapdor, Matthias Kalder, Elena I Braicu, Sophie Fürst, Maximilian Klar, Hans-Georg Strauß, Katharina Prieske, Linn Wölber. Prognostic impact of immune cells in vulvar carcinomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6485.