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纳秒脉冲电场通过 NK-CD103(+) DC 交互作用刺激肿瘤微环境中 CD103(+) DC 积聚

英文原题:Nanosecond pulsed electric field stimulates CD103(+) DC accumulation in tumor microenvironment via NK-CD103(+) DC crosstalk.

查看英文原题

Nanosecond pulsed electric field stimulates CD103(+) DC accumulation in tumor microenvironment via NK-CD103(+) DC crosstalk.

PubMed 2023/11/28(内容时间) Cancer Lett Q1 · IF 11.8(JCR 2025)

分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。

中文摘要

CD103+ DC对抗肿瘤免疫应答至关重要。作为一种有前景的癌症局部治疗方法,纳秒脉冲电场(nsPEF)已被广泛报道可刺激抗肿瘤免疫应答,但瘤内CD103+ DC与nsPEF治疗之间的潜在关系仍不明确。

在此,我们聚焦于CD103+ DC对nsPEF治疗的反应行为,并探索其潜在机制。我们发现,nsPEF治疗导致肿瘤中CD103+ DC的活化和积聚。通过Batf3-/-小鼠清除CD103+ DC证明,CD103+ DC对于nsPEF治疗引起的瘤内CD8+ T细胞浸润和活化是必需的。

值得注意的是,NK细胞通过CCL5将CD103+ DC募集到nsPEF治疗的肿瘤中。炎症因子阵列显示,CD103+ DC来源的IL-12介导了NK细胞中CCL5的分泌。

此外,cGAS-STING通路抑制后,瘤内CD103+ DC增强的活化和浸润被消除,随后IL-12和CCL5降低。进一步地,nsPEF治疗促进CD103+ DC介导的抗肿瘤应答,增强了CD47阻断策略的效果。

总之,本研究揭示了CD103+ DC在nsPEF治疗引发的抗肿瘤免疫应答中前所未有的作用,并阐明了其潜在机制。

展开英文摘要原文

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.

论文信息

作者
Qian J、Ding L、Wu Q、Yu X、Li Q、Gu Y、Wang S、Mao J
第一作者单位
Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Key Laboratory of Organ Transplantation, Zhejiang Province, China; Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment for Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Sciences(2019RU019), China; State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, China.China
通讯作者单位
Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Key Laboratory of Organ Transplantation, Zhejiang Province, China; Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment for Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Sciences(2019RU019), China; State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, China; Department of Hepatobiliary and Pancreatic Surgery, Department of Liver Transplantation, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou, 310000, China. Electronic address: shusenzheng@zju.edu.cn.China
文献类型
非美国政府资助研究
期刊
Cancer letters2024 Jul 1
原文标识
PubMed 38036040 · DOI 10.1016/j.canlet.2023.216514