Stromal infiltrating mast cells identify immunoevasive subtype high-grade serous ovarian cancer with poor prognosis and inferior immunotherapeutic response.
Tumor infiltrating mast cells (TIMs), with pro- or anti-tumorigenic role in different types of malignancies, have been implicated in resistance to anti-PD1 therapy. Here, we aimed to identify the relevance of TIMs with the prognosis, immune contexture, and immunotherapy in high-grade serous ovarian cancer (HGSOC). Tissue microarrays containing 197 HGSOC patients were assessed by immunohistochemistry (IHC) for detecting the expression of mast cell tryptase and other immune markers. Kaplan-Meier curve, log-rank test, and Cox regression model were applied to perform survival analysis. Single-cell RNA-seq analysis and flow cytometric analysis were selected to characterize TIMs. Furthermore, short-term HGSOC organoids were employed to validate the effect of TIMs on anti-PD1 therapy. Abundance of stromal TIMs (sTIMs) predicted dismal prognosis and linked to immunoevasive subtype of HGSOC, characterized by increased infiltration of pro-tumor cells (Treg cells, M2-polarized macrophages, and neutrophils) and impaired anti-tumor immune functions. Intensive inter-cell interactions between TIMs and other immune cells were identified, suggesting potential cross-talks to foster an immunosuppressive microenvironment. Organoids derived from sTIMs-low patients were associated with increased response to anti-PD-1 treatment other than the presence of high sTIMs infiltration. A nomogram, constructed by combining FIGO stage, sTIMs, and PD-L1, with an area under the curve (AUC) for predicting 5-year overall survival of 0.771 was better than that of FIGO staging system of 0.619. sTIMs/PD-L1-based classifier has potential clinical application in predicting prognosis of patients with HGSOC. sTIMs-high tumors correlate with immunosuppressive tumor microenvironment (TME) and possess potential insensitivity to immunotherapy.
['Cao|Kankan|K|', 'Zhang|Guodong|G|', 'Zhang|Xiangyun|X|', 'Yang|Moran|M|', 'Wang|Yiying|Y|', 'He|Mengdi|M|', 'Lu|Jiaqi|J|', 'Liu|Haiou|H|0000-0003-0200-8981']
D018284:Cystadenocarcinoma, Serous D005260:Female D006801:Humans D007167:Immunotherapy D008407:Mast Cells D010051:Ovarian Neoplasms D011379:Prognosis D059016:Tumor Microenvironment
High-grade serous ovarian cancer prognosis tumor infiltrating mast cell immunotherapy tumor microenvironment