肿瘤细胞治疗研究
英文原题：Placenta-derived trophoblast extracellular vesicles promote CD169(+) macrophage migration and suppress ovarian tumour growth.
胎盘来源的滋养层细胞EVs可能作为一种免疫调节剂，特别是在肿瘤存在的情况下，通过促进CD169+巨噬细胞向肿瘤部位募集，从而产生抗卵巢肿瘤应答。这些发现提示滋养层细胞EVs作为一种新型免疫治疗策略的潜力。
由于诊断时分期较晚导致生存率较低，卵巢癌需要更有效的治疗方法。细胞外囊泡（EVs）在多种疾病中显示出治疗潜力，部分原因在于其调节免疫反应的能力。我们此前的研究表明，胎盘来源的滋养细胞EVs可抑制卵巢肿瘤生长，并伴有肿瘤中CD169+巨噬细胞和NK细胞浸润增加。然而，其潜在机制尚不清楚。本研究探讨了体内免疫细胞如何响应胎盘来源的滋养细胞EVs迁移至肿瘤。
对SKOV-3卵巢癌细胞异种移植瘤经腹腔注射胎盘源性滋养层细胞EVs。监测肿瘤生长情况，并在四个时间点追踪EV的生物分布。此外，分析了免疫器官和肿瘤组织中CD169 + 巨噬细胞和NK细胞的动态变化。
观察到EV治疗后肿瘤生长减少。在早期时间点（24小时内），滋养层EV优先蓄积于免疫器官，包括腹股沟淋巴结，而非肿瘤中。与对照组相比，24小时内腹股沟淋巴结中CD169 + 巨噬细胞的强度显著更高。然而，到第30天，肿瘤中观察到EV和CD169 + 巨噬细胞的浸润，且存在明显的共定位。此外，早期时间点未观察到NK细胞浸润，但在第30天于腹股沟淋巴结中观察到NK细胞浸润，同时IL-15（一种已知的NK细胞激活因子）增加。重要的是，在给予EV治疗的非荷瘤小鼠中，与对照组相比，未观察到腹股沟淋巴结中CD169 + 巨噬细胞的浸润。
BACKGROUND: A lower survival rate due to a later stage of diagnosis requires a more effective therapy for ovarian cancer. Extracellular vesicles (EVs) have shown therapeutic potential in various diseases, partly due to their ability to modulate immune responses. We previously showed that placental-derived trophoblast EVs suppressed ovarian tumour growth, accompanied by increased infiltration of CD169 + macrophages and NK cells in tumours. However, the underlying mechanism is unclear. Here, we investigated how immune cells migrate to tumors in response to placental-derived trophoblast EVs in vivo. METHOD: SKOV-3 ovarian cancer cell xenografts were intraperitoneally injected with placental-derived trophoblast EVs. Tumour growth was monitored, and EV biodistribution was tracked at four time points. Additionally, the dynamics of CD169 + macrophages and NK cells were analysed in immune organs and tumour tissues. RESULTS: A reduction of tumour growth after EV treatment was observed. At early time points (within 24 hours), trophoblast EVs preferentially accumulated in immune organs, including the inguinal lymph nodes, but not in tumours. The significantly higher intensity of CD169 + macrophages was observed in the inguinal lymph nodes within 24 hours, compared to controls. However, by day 30, the infiltration of EVs and CD169 + macrophages was observed in tumours, with clear colocalization. Additionally, no infiltration of NK cells was observed at early time points, but was observed at day 30 in the inguinal lymph nodes, with the increase in IL-15, a known NK cell activator. Importantly, in non-tumour-bearing mice following EV treatment, the infiltration of CD169 + macrophages in the inguinal lymph nodes was not observed, compared to controls. CONCLUSION: Placental-derived trophoblast EVs may act as an immune modulator, specifically in the presence of tumours, through promoting CD169 + macrophage recruitment to the tumour site, resulting in an anti-ovarian tumour response. These findings suggest the potential of trophoblast EVs as a novel immune-based therapeutic strategy.
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