通过靶向肿瘤相关巨噬细胞的嵌合受体工程化溶瘤病毒重振内源性抗肿瘤免疫
Rejuvenating endogenous antitumor immunity via a chimeric receptor-engineered oncolytic virus targeting tumor-associated macrophages.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
溶瘤病毒 M1 作为双功能检查点抑制剂增强 DC 疫苗的抗肿瘤活性
英文原题：Oncolytic virus M1 functions as a bifunctional checkpoint inhibitor to enhance the antitumor activity of DC vaccine.
查看英文原题
Oncolytic virus M1 functions as a bifunctional checkpoint inhibitor to enhance the antitumor activity of DC vaccine.
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中文摘要
尽管树突状细胞（DC）疫苗前景广阔，但其临床获益仍然有限，主要归因于免疫抑制性肿瘤微环境（TME）以及肿瘤相关抗原（TAA）的缺乏。溶瘤病毒治疗是克服免疫抑制并暴露TAA的理想策略；因此，它们可能与DC疫苗产生协同作用。在本研究中，我们证明溶瘤病毒M1（OVM）能够通过增加TME中CD8+效应T细胞的浸润，在多种同系小鼠肿瘤模型中增强DC疫苗的抗肿瘤效果。在机制上，我们表明肿瘤细胞通过SIRPα-CD47免疫检查点对抗DC疫苗，而OVM能够下调DCs中的SIRPα和肿瘤细胞中的CD47。由于OVM上调DCs中的PD-L1，将PD-L1阻断与DC疫苗和OVM联合使用可进一步增强抗肿瘤活性。总体而言，OVM通过靶向SIRPα-CD47轴增强DC疫苗的抗肿瘤疗效，该轴对DC疫苗发挥主导性免疫抑制作用。
展开英文摘要原文
Although promising, dendritic cell (DC) vaccines still provide limited clinical benefits, mainly due to the immunosuppressive tumor microenvironment (TME) and the lack of tumor-associated antigens (TAAs). Oncolytic virus therapy is an ideal strategy to overcome immunosuppression and expose TAAs; therefore, they may work synergistically with DC vaccines.
In this study, we demonstrate that oncolytic virus M1 (OVM) can enhance the antitumor effects of DC vaccines across diverse syngeneic mouse tumor models by increasing the infiltration of CD8 + effector T cells in the TME. Mechanically, we show that tumor cells counteract DC vaccines through the SIRPα-CD47 immune checkpoint, while OVM can downregulate SIRPα in DCs and CD47 in tumor cells. Since OVM upregulates PD-L1 in DCs, combining PD-L1 blockade with DC vaccines and OVM further enhances antitumor activity.
Overall, OVM strengthens the antitumor efficacy of DC vaccines by targeting the SIRPα-CD47 axis, which exerts dominant immunosuppressive effects on DC vaccines.
论文信息
- 作者
- Dan J、Cai J、Zhong Y、Wang C、Huang S、Zeng Y、Fan Z、Xu C
- 第一作者单位
- Advanced Medical Technology Center, The First Affiliated Hospital-Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China; Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China; Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.China
- 通讯作者单位
- Advanced Medical Technology Center, The First Affiliated Hospital-Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China; Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China. Electronic address: liny96@mail.sysu.edu.cn.China
- 文献类型
- 非美国政府资助研究
- 期刊
- Cell reports. Medicine2023 Oct 17
- 原文标识
- PubMed 37820722 · DOI 10.1016/j.xcrm.2023.101229
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