Abstract B089: Intratumoral expression analysis of mast cells in high grade serous ovarian cancer

Abstract Objective: The goal of this study is to examine intratumoral expression and phenotypic changes in mast cells following neoadjuvant chemotherapy (NACT) exposure in high grade serous ovarian cancer (HGSOC). Methods: 37 HGSOC matched pre-and post-NACT patient tumors were stained with a commercially available mast cell hemotoxic-based kit and both intratumoral and stromal mast cells were quantified. Immunohistochemistry was employed to stain for histamine in 19 matched HGSOC patient tumors and mean intensity and integrated optical density was quantified using Image J. Kaplan Meier curve analysis was employed to determine the relationship between mast cells levels and progression-free survival (PFS). Immortalized human mast cells, LUVA were treated with carboplatin and paclitaxel and specific genomic changes were measured by quantitative PCR (qPCR). Results. Mast cells were more prominently expressed in intraepithelial regions compared to stromal cells, however both populations were significantly (p<0.05) increased following NACT. Total mast cells stratified by upper and lower quartile demonstrated that higher levels were significantly (p<0.05) associated with improved PFS. Furthermore, histamine, a marker of mast cell degranulation was significantly (p<0.05) increased in HGSOC tumors post-NACT and significantly correlated (r=0.553, p=0.013) with the change in total mast cells. Following chemotherapy treatment LUVA cells demonstrated an over 7-fold increase in amphiregulin (AREG) expression (p<0.01), a key marker of mast cell activation. Interestingly, angiogenic and pro-tumorigenic factors IL-10, IL-8, and VEGFA exhibited no significant differences in expression following chemotherapy exposure. Conclusions: Overall, our findings suggest a correlation in NACT exposure and intratumoral mast cell recruitment, degranulation, and activation. Further studies include investigating differences in specific tumorigenic genes and cell signaling pathways in mast cells pre- and post- NACT, as well as determining if mast cells can impact HGSOC chemotherapy response. Citation Format: Julia McAdams, Jasmine Ebott, Payton De La Cruz, Nicole E. James. Intratumoral expression analysis of mast cells in high grade serous ovarian cancer [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr B089.