免疫系统
癌症研究
癌症免疫疗法
免疫疗法
癌症
癌细胞
免疫检查点
免疫学
生物
遗传学
作者
Yifei Lü,Kristin Huntoon,DaeYong Lee,Yifan Wang,JongHoon Ha,Yaqing Qie,Xuefeng Li,Benjamin R. Schrank,Shiyan Dong,Thomas D. Gallup,Minjeong Kang,Zhao Hai,Yi An,Zhaogang Yang,Jing Li,Betty Y.S. Kim,Wen Jiang
标识
DOI:10.1038/s41565-022-01245-7
摘要
Solid tumours display a limited response to immunotherapies. By contrast, haematological malignancies exhibit significantly higher response rates to immunotherapies as compared with solid tumours. Among several microenvironmental and biological disparities, the differential expression of unique immune regulatory molecules contributes significantly to the interaction of blood cancer cells with immune cells. The self-ligand receptor of the signalling lymphocytic activation molecule family member 7 (SLAMF7), a molecule that is critical in promoting the body's innate immune cells to detect and engulf cancer cells, is expressed nearly exclusively on the cell surface of haematologic tumours, but not on solid ones. Here we show that a bispecific nanobioconjugate that enables the decoration of SLAMF7 on the surface of solid tumours induces robust phagocytosis and activates the phagocyte cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes (cGAS-STING) pathway, sensitizing the tumours to immune checkpoint blockade. Our findings support an immunological conversion strategy that uses nano-adjuvants to improve the effectiveness of immunotherapies for solid tumours.
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