1. Nanosecond pulsed electric field stimulates CD103+ DC accumulation in tumor microenvironment via NK-CD103+ DC crosstalk.
- Author
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Qian, Junjie, Ding, Limin, Wu, Qinchuan, Yu, Xizhi, Li, Qiyong, Gu, Yangjun, Wang, Shuai, Mao, Jing, Liu, Xi, Li, Bohan, Pan, Caixu, Wang, Wenchao, Wang, Yubo, Liu, Jianpeng, Qiao, Yiting, Xie, Haiyang, Chen, Tianchi, Ge, Jiangzhen, Zhou, Lin, and Yin, Shengyong
- Subjects
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ELECTRIC fields , *TUMOR microenvironment , *KILLER cells , *T cells , *CD47 antigen - Abstract
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. • CD103+ DC is necessary for antitumor immune response induced by nsPEF treatment. • NsPEF treatment leads to activation of intratumoral CD103+ DC. • NsPEF treatment induces the recruitment of CD103+ DC via IL12-NK-CCL5 axis. • CGAS-STING pathway controls activation and recruitment of CD103+ DC. • CD47 blockade promotes nsPEF-mediated activation and recruitment of CD103+ DC. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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