免疫系统
免疫疗法
癌症研究
乳酸乳球菌
癌症免疫疗法
免疫学
生物
癌症
接种疫苗
病毒学
配体(生物化学)
医学
计算生物学
微生物学
受体
细菌
乳酸
遗传学
作者
Junmeng Zhu,Yaohua Ke,Qin Liu,Ju Yang,Fangcen Liu,Ruihan Xu,Hang Zhou,Aoxing Chen,Jie Xiao,Fanyan Meng,Lixia Yu,Rutian Li,Jia Wei,Baorui Liu
标识
DOI:10.1038/s41467-022-35130-7
摘要
Abstract In situ vaccination is a promising strategy to convert the immunosuppressive tumor microenvironment into an immunostimulatory one with limited systemic exposure and side effect. However, sustained clinical benefits require long-term and multidimensional immune activation including innate and adaptive immunity. Here, we develop a probiotic food-grade Lactococcus lactis -based in situ vaccination (FOLactis) expressing a fusion protein of Fms-like tyrosine kinase 3 ligand and co-stimulator OX40 ligand. Intratumoural delivery of FOLactis contributes to local retention and sustained release of therapeutics to thoroughly modulate key components of the antitumour immune response, such as activation of natural killer cells, cytotoxic T lymphocytes, and conventional-type-1-dendritic cells in the tumors and tumor-draining lymph nodes. In addition, intratumoural administration of FOLactis induces a more robust tumor antigen-specific immune response and superior systemic antitumour efficacy in multiple poorly immune cell-infiltrated and anti-PD1-resistant tumors. Specific depletion of different immune cells reveals that CD8 + T and natural killer cells are crucial to the in situ vaccine-elicited tumor regression. Our results confirm that FOLactis displays an enhanced antitumour immunity and successfully converts the ‘cold’ tumors to ‘hot’ tumors.
科研通智能强力驱动
Strongly Powered by AbleSci AI