Affiliation:
1. CAS Key Lab for Biomedical Effects of Nanomaterials and Nanosafety Institute of High Energy Physics Chinese Academy of Sciences 19B YuquanLu, Shijingshan District Beijing 100049 China
2. University of Chinese Academy of Sciences Beijing 100049 China
3. State Key Laboratory for Quality Ensurance and Sustainable Use of Dao‐di Herbs Artemisinin Research Center and Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences Beijing 100700 China
4. Guangdong‐Hong Kong‐Macao Joint Laboratory for Neutron Scattering Science and Technology Spallation Neutron Source Science Center Dongguan 523803 China
Abstract
AbstractRadiated tumor cell‐derived extracellular vesicles (RT‐EVs) encapsulate abundant DNA fragments from irradiated tumor cells, in addition to acting as integrators of multiple tumor antigens. Accumulating evidence indicates these DNA fragments from damaged cells are involved in downstream immune responses, but most of them are degraded in cells before incorporation into derived RT‐EVs, thus the low abundance of DNA fragments limits immune responses of RT‐EVs. Here, this study found that different radiations affected fates of DNA fragments in RT‐EVs. Boron neutron capture therapy (BNCT) induced DNA accumulation in RT‐EVs (BEVs) by causing more DNA breaks and DNA oxidation resisting nuclease degradation. This is attributed to the high‐linear energy transfer (LET) properties of alpha particles from the neutron capture reaction of 10B. When being internalized by dendritic cells (DCs), BEVs activated the DNA sensing pathway, resulting in functional enhancements including antigen presentation, migration capacity, and cytokine secretion. After vaccination of the BEVs‐educated DCs (BEV@BMDCs), the effector T cells significantly expanded and infiltrated into tumors, suggesting robust anti‐tumor immune activation. BEV@BMDCs not only effectively inhibited the primary tumor growth and metastasis formation but also elicited long‐term immune memory. In conclusion, a successful DC vaccine is provided as a promising candidate for tumor vaccine.
Funder
National Natural Science Foundation of China
National Basic Research Program of China
Basic and Applied Basic Research Foundation of Guangdong Province
Beijing Nova Program