乳腺癌易感基因1(BRCA1)相关的卵巢癌患者被使用聚(ADP-核糖)聚合酶(PARP)抑制剂治疗，进一步延长了无进展生存期; 然而，它们最终获得了治疗耐药性。白细胞介素(IL)-34 被报道为多种癌症，包括卵巢癌的不良预后因素，并贡献于化疗治疗学的治疗耐药性。IL-34 可能通过肿瘤微环境(TME)的调节影响 PARP 抑制剂的治疗效果。本研究使用 Cancer Genome Atlas (TCGA) 数据集评估了 IL-34 与人类卵巢浆液性癌的预后。在小鼠模型中，我们还使用 CRISPR-Cas9 基因编辑技术评估了在 IL-34 存在与否情况下 PARP 抑制剂疗法的疗效。我们发现，在卵巢浆液性癌中，IL-34 是一个独立的不良预后因素，其高表达显著缩短了总生存期。此外，在 BRCA1 相关卵巢癌中，PARP 抑制剂治疗通过 XCR1+ DC-CD8+ T 细胞轴有助于抗肿瘤免疫力，然而，它被 IL-34 的存在所取消。这些结果表明，肿瘤源性的 IL-34 通过创建免疫抑制的肿瘤微环境及提供 PARP 抑制剂治疗耐药性而对肿瘤有益。因此，我们展示了 IL-34 的病理作用及其作为卵巢癌治疗靶点的必要性。© 2023. 亚洲妇产肿瘤学会，韩国妇产肿瘤学会和日本妇产肿瘤学会。

Breast cancer susceptibility gene 1 (BRCA1)-associated ovarian cancer patients have been treated with A poly (ADP-ribose) polymerase (PARP) inhibitor, extending the progression-free survival; however, they finally acquire therapeutic resistance. Interleukin (IL)-34 has been reported as a poor prognostic factor in several cancers, including ovarian cancer, and it contributes to the therapeutic resistance of chemotherapies. IL-34 may affect the therapeutic effect of PARP inhibitor through the regulation of tumor microenvironment (TME).In this study, The Cancer Genome Atlas (TCGA) data set was used to evaluate the prognosis of IL-34 and human ovarian serous carcinoma. We also used CRISPR-Cas9 genome editing technology in a mouse model to evaluate the efficacy of PARP inhibitor therapy in the presence or absence of IL-34.We found that IL34 was an independent poor prognostic factor in ovarian serous carcinoma, and its high expression significantly shortens overall survival. Furthermore, in BRCA1-associated ovarian cancer, PARP inhibitor therapy contributes to anti-tumor immunity via the XCR1+ DC-CD8+ T cell axis, however, it is canceled by the presence of IL-34.These results suggest that tumor-derived IL-34 benefits tumors by creating an immunosuppressive TME and conferring PARP inhibitor therapeutic resistance. Thus, we showed the pathological effect of IL-34 and the need for it as a therapeutic target in ovarian cancer.© 2023. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.