The immunological implications of cuproptosis,a form of cell death highly sensitive to oxygen presence,remain largely unexplored in the context of tumor immunother-apy.Herein,we initially investigate the positive corr...The immunological implications of cuproptosis,a form of cell death highly sensitive to oxygen presence,remain largely unexplored in the context of tumor immunother-apy.Herein,we initially investigate the positive correlation between cuproptosis and tumor immunotherapy through bioinformatics analysis.Subsequently,an oxygen generator loaded with copper ions(Cu/APH-M)has been constructed,which serves as an effective carrier of copper ions and crucially enhances the oxygenation of the tumor microenvironment.Importantly,Cu/APH-M-mediated dual strengthening of cuproptosis and radiotherapy could not only trigger a powerful antitumor immunity related to immunogenic cell death by RNA-sequencing analysis,but also effec-tively inhibit the growth of both distal and in situ low rectal tumors after combined immunotherapy,creating a robust immune memory effect.Our work reveals the ben-eficial effects of enhanced cuproptosis in radio-immunotherapy and elucidates its underlying mechanisms,which provides a novel approach for the synergistic inte-gration of cuproptosis with immunotherapy and radiotherapy,broadening the scope of cuproptosis-mediated tumor therapy.展开更多
基金Natural Science Foundation of Jiangsu Province,Grant/Award Number:BK20190946Gusu Leading Talent Program for Innovation and Entrepreneurship,Grant/Award Number:ZXL2021441+5 种基金Suzhou health youth backbone talent“national tutorial system”training project,Grant/Award Number:Qngg2023005Key Research and Development Program of Social Development of Jiangsu Province,Grant/Award Number:BE2022725Natural Science Foundation of Anhui Province,Grant/Award Number:2308085QH281Beijing Sisko Clinical Oncology Research Foundation,Grant/Award Number:Y-tongshu2021/qn-0366Key Scientific Research Project of Colleges and Universities of Anhui Province of China,Grant/Award Number:2022AH050683National Natural Science Foundation of China,Grant/Award Numbers:12275003,32171382,32301169,U1932208。
文摘The immunological implications of cuproptosis,a form of cell death highly sensitive to oxygen presence,remain largely unexplored in the context of tumor immunother-apy.Herein,we initially investigate the positive correlation between cuproptosis and tumor immunotherapy through bioinformatics analysis.Subsequently,an oxygen generator loaded with copper ions(Cu/APH-M)has been constructed,which serves as an effective carrier of copper ions and crucially enhances the oxygenation of the tumor microenvironment.Importantly,Cu/APH-M-mediated dual strengthening of cuproptosis and radiotherapy could not only trigger a powerful antitumor immunity related to immunogenic cell death by RNA-sequencing analysis,but also effec-tively inhibit the growth of both distal and in situ low rectal tumors after combined immunotherapy,creating a robust immune memory effect.Our work reveals the ben-eficial effects of enhanced cuproptosis in radio-immunotherapy and elucidates its underlying mechanisms,which provides a novel approach for the synergistic inte-gration of cuproptosis with immunotherapy and radiotherapy,broadening the scope of cuproptosis-mediated tumor therapy.
