促进疫苗接种方法诱导肺部记忆CD8+ T细胞衍生自预防肿瘤肺转移的中心记忆T细胞
A Prime-Boost Vaccination Approach Induces Lung Resident Memory CD8+ T Cells Derived from Central Memory T Cells That Prevent Tumor Lung Metastasis
影响因子:16.60000
分区:医学1区 Top / 肿瘤学1区
发表日期:2024 Oct 01
作者:
Haoran Xu, Ming Yue, Runhong Zhou, Pui Wang, Michael Yik-Chun Wong, Jinlin Wang, Huarong Huang, Bohao Chen, Yufei Mo, Rachel Chun-Yee Tam, Biao Zhou, Zhenglong Du, Haode Huang, Li Liu, Zhiwu Tan, Kwok-Yung Yuen, Youqiang Song, Honglin Chen, Zhiwei Chen
摘要
记忆T细胞在免疫保护癌症中起关键作用。疫苗诱导的组织驻留记忆T（TRM）细胞已显示可预防肺转移。鉴定肺TRM细胞的来源可以帮助改善策略，以防止肿瘤转移。在这里，我们发现使用肌内DNA疫苗启动的促进疫苗接种方法，其次是鼻内活性流感疫苗反射疫苗（LAIV）促进诱导较高的肺CD8+ TRM细胞的较高频率。疫苗诱导的肺CD8+ TRM细胞，但没有循环记忆T细胞，对转移性黑色素瘤和间皮瘤进行了明显的保护。通过DNA疫苗接种诱导的中央记忆T（TCM）细胞是鼻内LAIV增强后建立的肺TRM细胞的主要前体。单细胞RNA测序分析表明，TCM细胞在LAIV促进后的第2天最早启动了TCM细胞以分化为TRM细胞的TCM细胞的转录重编程。鼻内LAIV改变了粘膜微环境，通过CXCR3依赖性趋化性趋势和诱导的CD8+ TRM相关转录程序募集TCM细胞。这些结果将TCM细胞确定为疫苗诱导的CD8+ TRM细胞的来源，可预防肺转移。意义：促进疫苗接种塑造粘膜微环境，并重新编程中央记忆T细胞以产生肺部记忆T细胞，以防止肺转移，从而为优化疫苗策略提供了见解。
Abstract
Memory T cells play a key role in immune protection against cancer. Vaccine-induced tissue-resident memory T (TRM) cells in the lung have been shown to protect against lung metastasis. Identifying the source of lung TRM cells can help to improve strategies, preventing tumor metastasis. Here, we found that a prime-boost vaccination approach using intramuscular DNA vaccine priming, followed by intranasal live-attenuated influenza-vectored vaccine (LAIV) boosting induced higher frequencies of lung CD8+ TRM cells compared with other vaccination regimens. Vaccine-induced lung CD8+ TRM cells, but not circulating memory T cells, conferred significant protection against metastatic melanoma and mesothelioma. Central memory T (TCM) cells induced by the DNA vaccination were major precursors of lung TRM cells established after the intranasal LAIV boost. Single-cell RNA sequencing analysis indicated that transcriptional reprogramming of TCM cells for differentiation into TRM cells in the lungs started as early as day 2 post the LAIV boost. Intranasal LAIV altered the mucosal microenvironment to recruit TCM cells via CXCR3-dependent chemotaxis and induced CD8+ TRM-associated transcriptional programs. These results identified TCM cells as the source of vaccine-induced CD8+ TRM cells that protect against lung metastasis. Significance: Prime-boost vaccination shapes the mucosal microenvironment and reprograms central memory T cells to generate lung resident memory T cells that protect against lung metastasis, providing insights for the optimization of vaccine strategies.