Downregulation of ANKRD22 promotes ovarian cancer cell proliferation by enhancing the immunosuppressive capacity of M-MDSCs

ANKRD22 is a protein involved in tumor immune regulation. To elucidate its role in ovarian cancer, we analyzed its expression pattern and association with the tumor immune microenvironment. Bioinformatics analyses revealed upregulation of ANKRD22 in ovarian cancer tissues compared with normal controls. High ANKRD22 expression correlated with favorable patient prognosis, suggesting its potential as a prognostic biomarker. In vitro experiments using the ID8 murine ovarian cancer cell line, selected for its relevance to immunocompetent mouse models in tumor microenvironment studies, revealed that ANKRD22 expression is regulated by the tumor microenvironment. Monocytic myeloid-derived suppressor cells (M-MDSCs) with Ankrd22 knockout exhibited enhanced immunosuppressive function, inhibited T lymphocyte proliferation and reduced IL-2 secretion. These M-MDSCs promoted ovarian cancer cell proliferation primarily through direct contact. RNA sequencing suggested that Ankrd22 might regulate the immunosuppressive function of M-MDSCs by modulating fatty acid metabolism. In vivo rescue experiments in a subcutaneous tumor model confirmed that Ankrd22 mediates the protumor effect of M-MDSCs. In summary, this study demonstrated that downregulation of ANKRD22 promotes ovarian cancer progression by enhancing the immunosuppressive function of M-MDSCs, providing a theoretical basis for targeting ANKRD22 in ovarian cancer treatment.