Nanosecond pulsed electric field stimulates CD103+ DC accumulation in tumor microenvironment via NK-CD103+ DC crosstalk
Nanosecond pulsed electric field stimulates CD103+ DC accumulation in tumor microenvironment via NK-CD103+ DC crosstalk
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DOI：
10.1016/j.canlet.2023.216514
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发表时间：
2024-05-25
期刊：
影响因子：
9.7
通讯作者：
Zheng，Shusen
中科院分区：
文献类型：
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作者：
Qian，Junjie;Ding，Limin;Zheng，Shusen
CD103+DC对抗肿瘤免疫应答至关重要。作为一种很有前景的局部肿瘤治疗方法，纳秒脉冲电场（nsPEF）已被广泛报道可刺激抗肿瘤免疫反应，但肿瘤内CD103+DC与nsPEF治疗之间的潜在关系仍是谜。在这里，我们重点研究了CD103+DC对nsPEF治疗的反应，并探讨了其潜在机制。我们发现nsPEF处理导致肿瘤中CD103+DC的激活和积累。通过Batf3−/−小鼠消耗CD103+DC证明CD103+DC对于肿瘤内CD8+T细胞浸润和激活是必要的，以响应nsPEF治疗。值得注意的是，NK细胞通过CCL5将CD103+DC招募到nspef治疗的肿瘤中。炎症阵列显示CD103+ dc源性IL-12介导NK细胞CCL5分泌。此外，随着IL-12和CCL5的降低，肿瘤内CD103+DC的活化和浸润被cGAS-STING通路抑制而消除。此外，nsPEF治疗促进CD103+ dc介导的抗肿瘤反应增强了CD47阻断策略的效果。总之，这项研究揭示了CD103+DC在nsPEF治疗引发的抗肿瘤免疫应答中的前所未有的作用，并阐明了其潜在的机制。
CD103+DC is crucial for antitumor immune response. As a promising local therapy on cancers, nanosecond pulsed electric field (nsPEF) has been widely reported to stimulate anti-tumor immune response, but the underlying relationship between intratumoral CD103+DC and nsPEF treatment remains enigmatic. Here, we focused on the behavior of CD103+DC in response to nsPEF treatment and explored the underlying mechanism. We found that the nsPEF treatment led to the activation and accumulation of CD103+DC in tumor. Depletion of CD103+DC via Batf3−/−mice demonstrated CD103+DC was necessary for intratumoral CD8+T cell infiltration and activation in response to nsPEF treatment. Notably, NK cells recruited CD103+DC into nsPEF-treated tumor through CCL5. Inflammatory array revealed CD103+DC-derived IL-12 mediated the CCL5 secretion in NK cells. In addition, the boosted activation and infiltration of intratumoral CD103+DC were abolished by cGAS-STING pathway inhibition, following IL-12 and CCL5 decreasing. Furthermore, nsPEF treatment promoting CD103+DC-mediated antitumor response enhanced the effects of CD47 blockade strategy. Together, this study uncovers an unprecedented role for CD103+DC in nsPEF treatment-elicited antitumor immune response and elucidates the underlying mechanisms.