Obesity usually exacerbates the immunosuppressive tumor microenvironment(ITME),hindering CD8+T cell infiltration and function,which further represents a significant barrier to the efficacy of immunotherapy.Herein,a mu...Obesity usually exacerbates the immunosuppressive tumor microenvironment(ITME),hindering CD8+T cell infiltration and function,which further represents a significant barrier to the efficacy of immunotherapy.Herein,a multifunctional liposomal system(CR-Lip)for encapsulating celastrol(CEL)was utilized to remodel obesity-related ITME and improve cancer immunotherapy,wherein Ginsenoside Rg3(Rg3)was detected interspersed in the phospholipid bilayer and its glycosyl exposed on the surface of the liposome.CR-Lip had a relatively uniform size(116.5 nm),facilitating favorable tumor tissue accumulation through the interaction between Rg3 and glucose transporter 1 overexpressed in obese tumor cells.Upon reaching the tumor region,CR-Lip was found to induce the immunogenic cell death(ICD)of HFD tumor cells.Notably,the level of PHD3 in HFD tumor cells was effectively boosted by CR-Lip to effectively block metabolic reprogramming and increase the availability of major free fatty acids fuel sources.In vivo,experiments studies revealed that the easy-obtained nano platform stimulated enhanced the production of various cytokines in tumor tissues,DC maturation,CD8+T-cell infiltration,and synergistic anticancer therapeutic potency with aPD-1(tumor inhibition rate=82.1%)towards obesity-related melanoma.Consequently,this study presented an efficacious approach to tumor immunotherapy in obese mice by encompassing tumor eradication,inducing ICD,and reprogramming metabolism.Furthermore,it offered a unique insight into a valuable attempt at the immunotherapy of obesity-associated related tumors.展开更多
基金support from the Public Platform of Pharmaceutical Research Center,Academy of Chinese Medical Science,Zhejiang Chinese Medical University.This work was supported by the National Natural Science Foundation of China(82174095)the Natural Science Foundation of Zhejiang Province(LZ22H290001,China)the Zhejiang Province Traditional Chinese Medicine Science and Technology Project(2023ZL362).
文摘Obesity usually exacerbates the immunosuppressive tumor microenvironment(ITME),hindering CD8+T cell infiltration and function,which further represents a significant barrier to the efficacy of immunotherapy.Herein,a multifunctional liposomal system(CR-Lip)for encapsulating celastrol(CEL)was utilized to remodel obesity-related ITME and improve cancer immunotherapy,wherein Ginsenoside Rg3(Rg3)was detected interspersed in the phospholipid bilayer and its glycosyl exposed on the surface of the liposome.CR-Lip had a relatively uniform size(116.5 nm),facilitating favorable tumor tissue accumulation through the interaction between Rg3 and glucose transporter 1 overexpressed in obese tumor cells.Upon reaching the tumor region,CR-Lip was found to induce the immunogenic cell death(ICD)of HFD tumor cells.Notably,the level of PHD3 in HFD tumor cells was effectively boosted by CR-Lip to effectively block metabolic reprogramming and increase the availability of major free fatty acids fuel sources.In vivo,experiments studies revealed that the easy-obtained nano platform stimulated enhanced the production of various cytokines in tumor tissues,DC maturation,CD8+T-cell infiltration,and synergistic anticancer therapeutic potency with aPD-1(tumor inhibition rate=82.1%)towards obesity-related melanoma.Consequently,this study presented an efficacious approach to tumor immunotherapy in obese mice by encompassing tumor eradication,inducing ICD,and reprogramming metabolism.Furthermore,it offered a unique insight into a valuable attempt at the immunotherapy of obesity-associated related tumors.
