研究动态
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载有PD-1抑制剂的树突状细胞负荷外泌体在不同时间点的联合治疗对肝细胞癌具有优越的抗肿瘤效果。

Combination therapy with dendritic cell loaded-exosomes supplemented with PD-1 inhibition at different time points have superior antitumor effect in hepatocellular carcinoma.

发表日期:2023 Sep 04
作者: Chunxiao Chang, Yanqing Pei, Chuangnian Zhang, Wenyu Zhang, Yibo Qin, Shengbin Shi
来源: Cell Death & Disease

摘要:

肝细胞癌(HCC)是导致癌症相关死亡的一种常见原因,并对传统治疗不敏感。DC-TEX和程序性死亡蛋白1(PD-1)抗体(Ab)的联合抗肿瘤效果在不同时间间隔内尚未进行研究。本研究建立了HCC模型,并以不同时间间隔使用DC-TEX单独或与PD-1 Ab联合治疗。此外,我们在BALB/c裸鼠中建立了原位HCC模型并恢复了T细胞。结果表明,在DC-TEX治疗后,PD-1+CD8+T细胞人群数量显著增加,CD8+T细胞数量的增加也是如此。在DC-TEX给药后的72小时内,CD8+T细胞数量增加。PD-1+CD8+T细胞的表现也是如此。随后,在不同时间点(0、24、72、96、120或168小时)输注PD-1 Ab与DC-TEX的联合治疗。令人惊讶的是,该联合治疗展示了强大的抗肿瘤效果,尤其是在72小时给予PD-1 Ab时更为明显。PD-1 Ab显著逆转了体外PD-1+CD8+T细胞的增殖能力,在72小时时通过刺激CD8+T细胞增殖和抑制T细胞耗竭实现了PD-1 Ab和DC-TEX的联合抗肿瘤效果。总之,我们的结果表明,DC-TEX和PD-1 Ab的联合显著抑制了小鼠HCC模型中的肿瘤生长,并且PD-1 Ab的给药时间影响着其抗肿瘤效果。© 2023. 作者,Springer-Verlag GmbH Germany的独家许可,Springer Nature的一部分。
Hepatocellular carcinoma (HCC), a prevalent cause of cancer-related deaths, is insensitive to traditional treatments. At different time intervals, the combined antitumor effects of DC-TEX and the programmed death protein 1 (PD-1) antibody (Ab) have not been investigated. In this study, HCC models were established and treated at different time intervals with DC-TEX alone or in combination with PD-1 Ab. In addition, we developed an orthotopic HCC model in BALB/c nude mice and restored T cells. Results demonstrated that the PD-1 + CD8 + T-cell population also increased significantly after DC-TEX treatment, in addition to the increased number of CD8 + T cells. The number of CD8 + T cells increased 72 h after DC-TEX administration. Similar observations were made for PD-1 + CD8 + T cells. Subsequently, PD-1 Ab was administered in combination with DC-TEX at different time points (0, 24, 72, 96, 120, or 168 h). Surprisingly, the combination treatment demonstrated a strong antitumor effect, which was very prominent when PD-1 Ab was administered at 72 h. PD-1 Ab significantly reversed the proliferative ability of PD-1 + CD8 + T cells at 72 h in vitro. The combined antitumor effects of PD-1 Ab and DC-TEX occurred mainly by stimulating CD8 + T cell proliferation and inhibiting T cell exhaustion. In conclusion, our results indicate that the combination of DC-TEX and PD-1 Ab significantly inhibits tumor growth in a murine HCC model and that the timing of PD-1 Ab administration impacts the antitumor effect.© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.