与 HRD 患者相比，PARPi 为 HRP 患者提供的临床益处较少。 PARPi 具有免疫调节功能。 NRT 疗法针对肿瘤新抗原，没有脱靶免疫毒性。我们在 HRP 卵巢癌小鼠模型中探讨了 Niraparib 和 NRT 在增强抗肿瘤活性方面的协同作用。在 C57BL/6 小鼠 ID8 卵巢癌模型中，通过转录组数据的免疫细胞浸润分析评估 Niraparib 对重塑 TIME 的作用。系统评价了 Niraparib、NRT 及其联合使用的抗肿瘤作用。为了证实 TIME 内 TIL、TAM 和趋化因子谱的变化，我们采用了免疫荧光成像和转录组测序分析。 Niraparib 增加了患有 ID8 卵巢癌的 C57BL/6 小鼠肿瘤组织中的 M1-TAM 并激活了 CD8 T 细胞。 GSEA显示，与未成熟DC和INFα、细胞因子和趋化因子相关的基因集在免疫特征、KEGG和GO基因集上显着富集，同时CCL5、CXCL9和CXCL10共同发挥主导作用。在动物试验中，联合组与尼拉帕尼组（P < 0.01）和对照组（P < 0.001）相比，肿瘤生长延迟，与单药组相比，生存期更长（P < 0.01）。重塑作用，然后在 HRP 卵巢癌模型中与 NRT 发挥协同抗肿瘤作用。我们的研究结果为 HRP 卵巢癌联合免疫治疗提供了新的思路和原理。版权所有 © 2024。由 Elsevier Inc. 出版。

PARPi offers less clinical benefit for HRP patients compared to HRD patients. PARPi has an immunomodulatory function. NRT therapy targets tumor neoantigens without off-target immune toxicity. We explored the synergy between Niraparib and NRT in enhancing antitumor activity in an HRP ovarian cancer mouse model.In the C57BL/6 mouse ID8 ovarian cancer model, the effect of Niraparib on reshaping TIME was evaluated by immune cell infiltration analysis of transcriptomic data. The antitumor effects of Niraparib, NRT, and their combined use were systematically evaluated. To corroborate alterations in TILs, TAMs, and chemokine profiles within the TIME, we employed immunofluorescence imaging and transcriptome sequencing analysis.Niraparib increased the M1-TAMs and activated CD8+ T cells in tumor tissues of C57BL/6 mice with ID8 ovarian cancer. GSEA showed that gene set associated with immature DC and INFα, cytokines and chemokines were significantly enriched in immune feature, KEGG and GO gene sets, meanwhile CCL5, CXCL9 and CXCL10 play dominant roles together. In the animal trials, combined group had a tumor growth delay compared with Niraparib group (P < 0.01) and control group (P < 0.001), and longer survival compared with the single agent group (P<0.01) .Niraparib could exert immune-reshaping effects, then acts synergistic antitumor effects with NRT in HRP ovarian cancer model. Our findings provide new ideas and rationale for combined immunotherapy in HRP ovarian cancer.Copyright © 2024. Published by Elsevier Inc.