高级别浆液性卵巢癌（HGSOC）是最致命的妇科恶性肿瘤，患者尚未对临床可用的免疫疗法产生有意义的反应。因此，迫切需要新的免疫靶点。我们过去的工作发现，在新辅助化疗 (NACT) 暴露后，HGSOC 患者肿瘤中肥大细胞的 mRNA 水平显着上调。因此，在当前的研究中，我们试图表征 NACT 暴露导致的肿瘤内肥大细胞表型变化，并确定这些适应如何与患者临床结果相关。采用血液免疫组织化学来确定 36 名匹配的治疗前和治疗后的肥大细胞水平。 NACT HGSOC 患者肿瘤。利用荧光免疫组织化学法分别鉴定 29 例和 20 例 NACT HGSOC 患者肿瘤中匹配的类胰蛋白酶（羧肽酶 A3 (CPA3)    以及组胺水平）。最后，用卡铂刺激人类永生化肥大细胞 LUVA通过定量 PCR 分析紫杉醇和基因组变化。 NACT 后，肿瘤上皮内和基质区域的血液学标记的肿瘤内肥大细胞显着上调，NACT 前肥大细胞水平较低与无进展情况的改善显着相关。组胺（肥大细胞脱颗粒的标志物）在 NACT 暴露后的肿瘤中同样上调。肿瘤的上皮内和基质区室中，而肿瘤基质区域中的类胰蛋白酶细胞显着上调。 NACT 后较低的类胰蛋白酶 / CPA3  细胞治疗水平与改善的总生存 (OS) 和 PFS 显着相关，而较高的类胰蛋白酶  肥大细胞与改善的 OS 相关。最后，化疗暴露后，肥大细胞激活因子 AREG 和 CCL2 显着上调，而肥大细胞激活抑制剂 TGFB1 在 LUVA 细胞中下调。肥大细胞数量增加以及激活和脱粒是 NACT 暴露的结果。 NACT 后肥大细胞与生存结果表现出不同的关联，这取决于颗粒分类。最终，肥大细胞代表了临床相关的假定 HGSOC 免疫靶点。© 2024。作者。

High grade serous ovarian cancer (HGSOC) is the most lethal gynecologic malignancy in which patients have still yet to respond meaningfully to clinically available immunotherapies. Hence, novel immune targets are urgently needed. Our past work has identified that mast cells are significantly upregulated at the mRNA level in HGSOC patient tumors following neoadjuvant chemotherapy (NACT) exposure. Therefore, in this current investigation we sought to characterize intratumoral mast cell phenotypic changes as a result of NACT exposure and determine how these adaptations are associated with patient clinical outcomes.Hematologic immunohistochemistry was employed to determine mast cell levels in 36 matched pre- and post-NACT HGSOC patient tumors. Fluorescent Immunohistochemistry was utilized to identify Tryptase+(carboxypeptidase A3 (CPA3) + mast cells as well as histamine levels in 29 and 20, respectively, matched pre- and post-NACT HGSOC patient tumors. Finally, human immortalized mast cells, LUVA were stimulated with carboplatin and paclitaxel and genomic changes were analyzed by quantitative PCR.Hematologic labeled intratumoral mast cells were significantly upregulated in the intraepithelial and stromal regions of the tumor, post-NACT. Lower levels of pre-NACT mast cells were significantly associated with an improved progression-free survival (PFS). Histamine, a marker of mast cell degranulation was similarly upregulated in post-NACT exposed tumors. Through the characterization of mast cell specific proteases Tryptase and CPA3, it was found that Tryptase+/ CPA3 + mast cells were significantly upregulated both in the intraepithelial and stromal compartments of the tumor, while Tryptase + cells were significantly upregulated in the stromal regions of the tumor. Lower post-NACT treated levels with Tryptase+/ CPA3 + cells were significantly associated with improved overall survival (OS) and PFS while higher Tryptase + mast cells were associated with improved OS. Finally, following chemotherapy exposure mast cell activating factors AREG and CCL2 were significantly upregulated while TGFB1, an inhibitor of mast cell activation was downregulated in LUVA cells.Enhanced mast cell numbers, as well as activation and degranulation are a consequence of NACT exposure. Post-NACT mast cells displayed differing associations with survival outcomes that was dependent upon granule classification. Ultimately, mast cells represent a clinically relevant putative HGSOC immune target.© 2024. The Author(s).