Remodeling the tumor microenvironment through reprogramming tumor-associated macrophages(TAMs) and increasing the immunogenicity of tumors via immunogenic cell death(ICD) have been emerging as promising anticancer imm...Remodeling the tumor microenvironment through reprogramming tumor-associated macrophages(TAMs) and increasing the immunogenicity of tumors via immunogenic cell death(ICD) have been emerging as promising anticancer immunotherapy strategies.However,the heterogeneous distribution of TAMs in tumor tissues and the heterogeneity of the tumor cells make the immune activation challenging.To overcome these dilemmas,a hybrid bacterium with tumor targeting and penetration,TAM polarization,and photo thermal conversion capabilities is developed for improving antitumor immunotherapy in vivo.The hybrid bacteria(B.b@QDs) are prepared by loading Ag;S quantum dots(QDs) on the Bifidobacterium bifidum(B.b) through electrostatic interactions.The hybrid bacteria with hypoxia targeting ability can effectively accumulate and penetrate the tumor tissues,enabling the B.b to fully contact with the TAMs and mediate their polarization toward M1 phenotype to reverse the immunosuppressive tumor microenvironment.It also enables to overcome the intratumoral heterogeneity and obtain abundant tumor-associated antigens by coupling tumor penetration of the B.b with photo thermal effect of the QDs,resulting in an enhanced immune effect.This strategy that combines B.b-triggered TAM polarization and QD-induced ICD achieved a remarkable inhibition of tumor growth in orthotopic breast cancer.展开更多
基金supported by the National Natural Science Foundation of China(51725303,81701831,52033007)the Sichuan Science and Technology Program(2020YFH0046,China)the Fundamental Research Funds for the Central Universities(2682021CG017,China)。
文摘Remodeling the tumor microenvironment through reprogramming tumor-associated macrophages(TAMs) and increasing the immunogenicity of tumors via immunogenic cell death(ICD) have been emerging as promising anticancer immunotherapy strategies.However,the heterogeneous distribution of TAMs in tumor tissues and the heterogeneity of the tumor cells make the immune activation challenging.To overcome these dilemmas,a hybrid bacterium with tumor targeting and penetration,TAM polarization,and photo thermal conversion capabilities is developed for improving antitumor immunotherapy in vivo.The hybrid bacteria(B.b@QDs) are prepared by loading Ag;S quantum dots(QDs) on the Bifidobacterium bifidum(B.b) through electrostatic interactions.The hybrid bacteria with hypoxia targeting ability can effectively accumulate and penetrate the tumor tissues,enabling the B.b to fully contact with the TAMs and mediate their polarization toward M1 phenotype to reverse the immunosuppressive tumor microenvironment.It also enables to overcome the intratumoral heterogeneity and obtain abundant tumor-associated antigens by coupling tumor penetration of the B.b with photo thermal effect of the QDs,resulting in an enhanced immune effect.This strategy that combines B.b-triggered TAM polarization and QD-induced ICD achieved a remarkable inhibition of tumor growth in orthotopic breast cancer.
