Highly immunosuppressive tumor microenvironment containing various protumoral immune cells accelerates malignant transformation and treatment resistance.In particular,tumor-associated macrophages(TAMs),as the predomin...Highly immunosuppressive tumor microenvironment containing various protumoral immune cells accelerates malignant transformation and treatment resistance.In particular,tumor-associated macrophages(TAMs),as the predominant infiltrated immune cells in a tumor,play a pivotal role in regulating the immunosuppressive tumor microenvironment.As a potential therapeutic strategy to counteract TAMs,here we explore an exosome-guided in situ direct reprogramming of tumor-supportive M2-polarized TAMs into tumor-attacking M1-type macrophages.Exosomes derived from M1-type macrophages(M1-Exo)promote a phenotypic switch from anti-inflammatory M2-like TAMs toward pro-inflammatory M1-type macrophages with high conversion efficiency.Reprogrammed M1 macrophages possessing protein-expression profiles similar to those of classically activated M1 macrophages display significantly increased phagocytic function and robust cross-presentation ability,potentiating antitumor immunity surrounding the tumor.Strikingly,these M1-Exo also lead to the conversion of human patient-derived TAMs into M1-like macrophages that highly express MHC class II,offering the clinical potential of autologous and allogeneic exosome-guided direct TAM reprogramming for arming macrophages to join the fight against cancer.展开更多
We previously demonstrated that octadecylamine-functionalized nanodiamond(ND-ODA)and dexamethasone(Dex)-adsorbed ND-ODA(ND-ODA–Dex)promoted anti-inflammatory and proregenerative behavior in human macrophages in vitro...We previously demonstrated that octadecylamine-functionalized nanodiamond(ND-ODA)and dexamethasone(Dex)-adsorbed ND-ODA(ND-ODA–Dex)promoted anti-inflammatory and proregenerative behavior in human macrophages in vitro.In this study,we performed a pilot study to investigate if these immunomodulatory effects translate when used as a treatment for rheumatoid arthritis in mice.Following local injection in limbs of mice with collagen type II-induced arthritis,microcomputed tomography showed that mice treated with a low dose of ND-ODA and ND-ODA–Dex did not experience bone loss to the levels observed in non-treated arthritic controls.A low dose of ND-ODA and ND-ODA–Dex also reduced macrophage infiltration and expression of proinflammatory mediators iNOS and tumor necrosis factor-a compared to the arthritic control,while a high dose of ND-ODA increased expression of these markers.Overall,these results suggest that ND-ODA may be useful as an inherently immunomodulatory platform,and support the need for an in-depth study,especially with respect to the effects of dose.展开更多
基金This work was supported by the Samsung Research Funding&Incubation Center of Samsung Electronics(SRFC-MA1901-10)and the Intramural Research Program of KIST.
文摘Highly immunosuppressive tumor microenvironment containing various protumoral immune cells accelerates malignant transformation and treatment resistance.In particular,tumor-associated macrophages(TAMs),as the predominant infiltrated immune cells in a tumor,play a pivotal role in regulating the immunosuppressive tumor microenvironment.As a potential therapeutic strategy to counteract TAMs,here we explore an exosome-guided in situ direct reprogramming of tumor-supportive M2-polarized TAMs into tumor-attacking M1-type macrophages.Exosomes derived from M1-type macrophages(M1-Exo)promote a phenotypic switch from anti-inflammatory M2-like TAMs toward pro-inflammatory M1-type macrophages with high conversion efficiency.Reprogrammed M1 macrophages possessing protein-expression profiles similar to those of classically activated M1 macrophages display significantly increased phagocytic function and robust cross-presentation ability,potentiating antitumor immunity surrounding the tumor.Strikingly,these M1-Exo also lead to the conversion of human patient-derived TAMs into M1-like macrophages that highly express MHC class II,offering the clinical potential of autologous and allogeneic exosome-guided direct TAM reprogramming for arming macrophages to join the fight against cancer.
基金the National Institutes of Health grant R01 HL130037.A.P.was supported by Whitaker International and David L.Boren fellowships.
文摘We previously demonstrated that octadecylamine-functionalized nanodiamond(ND-ODA)and dexamethasone(Dex)-adsorbed ND-ODA(ND-ODA–Dex)promoted anti-inflammatory and proregenerative behavior in human macrophages in vitro.In this study,we performed a pilot study to investigate if these immunomodulatory effects translate when used as a treatment for rheumatoid arthritis in mice.Following local injection in limbs of mice with collagen type II-induced arthritis,microcomputed tomography showed that mice treated with a low dose of ND-ODA and ND-ODA–Dex did not experience bone loss to the levels observed in non-treated arthritic controls.A low dose of ND-ODA and ND-ODA–Dex also reduced macrophage infiltration and expression of proinflammatory mediators iNOS and tumor necrosis factor-a compared to the arthritic control,while a high dose of ND-ODA increased expression of these markers.Overall,these results suggest that ND-ODA may be useful as an inherently immunomodulatory platform,and support the need for an in-depth study,especially with respect to the effects of dose.
