Cisplatin nanoparticles boost abscopal effect of radiation plus anti-PD1 therapy.
Cisplatin nanoparticles boost abscopal effect of radiation plus anti-PD1 therapy.
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DOI：
10.1039/d1bm00112d
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发表时间：
2021-03
影响因子：
6.6
通讯作者：
Ying Wang;N. Shen;Yue Wang;Mo Li;Wanze Zhang;Liwen Fan;Linlin Liu;Zhaohui Tang;Xuesi Chen
中科院分区：
文献类型：
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作者：
Ying Wang;N. Shen;Yue Wang;Mo Li;Wanze Zhang;Liwen Fan;Linlin Liu;Zhaohui Tang;Xuesi Chen
放射治疗（RT）的远位效应具有临床意义，但很少发生。尽管抗程序性细胞死亡蛋白1抗体（抗PD 1）可能会增强接受RT的患者的远位效应，但发生率仍低于30%。一个主要的限制是在未照射的肿瘤内缺乏CD 8 + T细胞。在此，顺铂（CDDP）负载的聚（1-谷氨酸）-接枝-甲氧基聚（乙二醇）复合物纳米颗粒（CDDP-NP）被证实增加未照射肿瘤内的CD 8 + T细胞，并增强RT加抗PD 1的远位效应，并且比CDDP更强。与RT和RT + CDDP相比，RT + CDDP-NP诱导更大的免疫原性细胞死亡（ICD），其中钙网蛋白+刘易斯肺癌（LLC）细胞的比例增加（16.47%、20.53%和27.03%），同时沿着更多的CD 8 + T细胞浸润到单侧LLC肿瘤模型中的CDDP-NP处理的照射的肿瘤中。在双侧LLC肿瘤模型中，RT + CDDP-NP显著诱导更多的趋化因子（C-X-C基序）配体10（CXCL 10）分泌（36.3、44.19和56.37 pg mL-1），这对应于未照射肿瘤中更大的CD 8 + T细胞浸润（0.19%、0.20%和0.72%）。最后，与RT +抗PD 1和RT +抗PD 1 + CDDP相比，RT +抗PD 1 + CDDP-NP更有力地显著抑制未照射肿瘤的生长，如分别为1141、1146和585 mm 3的肿瘤体积所示。这是第一项研究表明，CDDP-NPs可以增强RT诱导的免疫激活，并突破RT加抗PD 1诱导的远位效应的效率限制。
The abscopal effect of radiation therapy (RT) is clinically significant but occurs rarely. Although anti-programmed cell death protein 1 antibody (anti-PD1) is likely to enhance the abscopal effect in patients receiving RT, the incidence rate remains less than 30%. One major limitation is the paucity of CD8+ T cells within non-irradiated tumors. Here, cisplatin (CDDP) loaded poly(l-glutamic acid)-graft-methoxy poly(ethylene glycol) complex nanoparticles (CDDP-NPs) are confirmed to increase CD8+ T cells within non-irradiated tumors and boost the abscopal effect of RT plus anti-PD1, and more strongly than CDDP. Compared to RT and RT + CDDP, RT + CDDP-NPs induced greater immunogenic cell death (ICD) with enhanced proportion of Calreticulin+ Lewis lung cancer (LLC) cells (16.47%, 20.53% and 27.03%), along with which more CD8+ T cells were infiltrated into CDDP-NP treated irradiated tumors in the unilateral LLC tumor model. In the bilateral LLC tumor model, RT + CDDP-NPs significantly induced more chemokine (C-X-C motif) ligand 10 (CXCL10) secretion (36.3, 44.19 and 56.37 pg mL-1), which corresponded to greater CD8+ T cell infiltration in the non-irradiated tumors (0.19%, 0.20% and 0.72%). Finally, compared to RT + anti-PD1 and RT + anti-PD1 + CDDP, RT + anti-PD1 + CDDP-NPs significantly inhibited the growth of non-irradiated tumors more forcefully, as indicated by the respective tumor volumes of 1141, 1146 and 585 mm3. This is the first study to show that CDDP-NPs can amplify RT-induced immune activation and break through the efficiency limitation of the RT plus anti-PD1 induced abscopal effect.