Nanosecond pulsed electric field stimulates CD103+ DC accumulation in tumor microenvironment via NK-CD103+ DC crosstalk
Junjie Qian, Limin Ding, Qinchuan Wu, Xizhi Yu, Qiyong Li, Yangjun Gu, Shuai Wang, Jing Mao, Xi Liu, Bohan Li, Caixu Pan, Wenchao Wang, Yubo Wang, Jianpeng Liu, Yiting Qiao, Haiyang Xie, Tianchi Chen, Jiangzhen Ge, Lin Zhou, Shengyong Yin, Shusen Zheng
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.