RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题: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.
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。
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。
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.
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