预注射外泌体可通过激活小鼠免疫系统显著抑制卵巢癌的生长。

IF 5.8 2区 医学 Q2 IMMUNOLOGY Cancer Immunology, Immunotherapy Pub Date : 2025-02-04 DOI:10.1007/s00262-025-03951-2
Yuanyuan Wang, Changyi Zhang, Huimin Zeng, Liangliang Wang, Zanhong Wang, Zhiqiang Han
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摘要

卵巢癌作为一种免疫细胞浸润有限的“冷肿瘤”,历来在免疫治疗中疗效有限。在这项研究中,我们报道了来自卵巢癌的外泌体可以特异性地靶向大网膜,而大网膜是卵巢癌转移和随后植入肿瘤的易发部位。此外,我们发现外泌体所在的大网膜组织中CD3 + T细胞的比例大幅增加,特别是CD8 + T细胞。这种增加伴随着CD8 + T细胞中颗粒酶B水平的显著增强。此外,外周血干扰素γ (IFN-γ)浓度显著升高。体外实验结果表明,外泌体可被树突状细胞内化,促进树突状细胞分化,进而诱导T细胞产生颗粒酶B和IFN-γ。令人惊讶的是,我们还观察到大网膜中程序性死亡配体1 (PD-L1)的高表达。因此,我们发现联合PD-L1阻断是否会导致肿瘤进一步消退。而联合组虽然肿瘤完全消退,但差异无统计学意义。但总的来说,我们强调,在预注射的情况下,外泌体通过靶向大网膜,激活抗肿瘤免疫,具有对抗著名的“冷肿瘤”卵巢癌的巨大潜力,为克服卵巢癌提供了新的途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Pre-injection of exosomes can significantly suppress ovarian cancer growth by activating the immune system in mice.

As a type of "cold tumor" with limited immune cell infiltration, ovarian cancer has historically shown limited efficacy in immunotherapy. In this study, we report that exosomes from ovarian cancer can specifically target omentum which is the predilection site for ovarian cancer to metastasize and combat subsequently implanted tumor. Furthermore, we found a substantial increase in the proportion of CD3 + T cells, particularly CD8 + T cells, within the omental tissue where exosomes homed. This increase was accompanied by a significant enhancement in granzyme B levels within CD8 + T cells. Additionally, there was a notable elevation in the concentration of interferon-gamma (IFN-γ) in peripheral blood. In vitro results indicated that exosomes could be internalized by dendritic cells (DCs), promote DC differentiation, and subsequently induce the production of granzyme B and IFN-γ in T cells. Surprisingly, we also observed high expression of programmed death ligand 1 (PD-L1) in the omentum. Therefore, we discovered whether combining PD-L1 blockade led to further tumor regression. However, although the combination group showed complete tumor regression, this difference did not reach statistical significance. But in general, we emphasize that in the case of pre-injection, exosomes have great potential to combat the famous "cold tumor", ovarian cancer, via targeting omentum and activating anti-tumor immunity, offering a novel avenue for overcoming ovarian cancer.

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来源期刊
CiteScore
10.50
自引率
1.70%
发文量
207
审稿时长
1 months
期刊介绍: Cancer Immunology, Immunotherapy has the basic aim of keeping readers informed of the latest research results in the fields of oncology and immunology. As knowledge expands, the scope of the journal has broadened to include more of the progress being made in the areas of biology concerned with biological response modifiers. This helps keep readers up to date on the latest advances in our understanding of tumor-host interactions. The journal publishes short editorials including "position papers," general reviews, original articles, and short communications, providing a forum for the most current experimental and clinical advances in tumor immunology.
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