CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Niraparib plays synergistic antitumor effects with NRT in a mouse ovarian cancer model with HRP.
Niraparib plays synergistic antitumor effects with NRT in a mouse ovarian cancer model with HRP.
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尼拉帕利可发挥免疫重塑作用，随后在 HRP 卵巢癌模型中与 NRT 产生协同抗肿瘤效应。我们的发现为 HRP 卵巢癌的联合免疫治疗提供了新思路和理论依据。
PARPi对HRP患者的临床获益不如HRD患者。PARPi具有免疫调节功能。NRT疗法靶向肿瘤新抗原，且无脱靶免疫毒性。我们在HRP卵巢癌小鼠模型中探索了Niraparib与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，通过对转录组数据进行免疫细胞浸润分析，评估了Niraparib对TIME重塑的影响。系统评估了Niraparib、NRT及其联合使用的抗肿瘤效果。为证实TIME中TILs、TAMs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。
尼拉帕利增加了ID8卵巢癌C57BL/6小鼠肿瘤组织中的M1-TAMs并激活了CD8+ T细胞。GSEA显示，与未成熟DC和INFα相关的基因集、细胞因子和趋化因子在免疫特征、KEGG和GO基因集中显著富集，同时CCL5、CXCL9和CXCL10共同发挥主导作用。在动物实验中，联合组与尼拉帕利组相比肿瘤生长延迟（P < 0.01），与对照组相比肿瘤生长延迟（P < 0.001），与单药组相比生存期更长（P<0.01）。
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.
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