Immunotherapy has great promise in improving malignant tumor treatment.However,the efficacy of existing strategies is often limited by the immunosuppressive environment.Here,we demonstrate an in situ bionic immunoacti...Immunotherapy has great promise in improving malignant tumor treatment.However,the efficacy of existing strategies is often limited by the immunosuppressive environment.Here,we demonstrate an in situ bionic immunoactivator,PLT-Bec1/DTA-1,with possessed natural advantages of platelets for tumor recruitment and activation,on which DTA-1(CD357 monoclonal antibody)and Bec1 were tethered as combined immune boosters.PLT-Bec1/DTA-1,as a self-triggered release repository,can deliver the pre-tethered Bec1 and DTA-1 deeply through the secretion of platelet microparticles(PMPs),thereby cooperate tacitly and exhibit superiority in immune activation of dendritic cells(DCs)and T cells via autophagy inducibility,coupled with glucocorticoid-induced tumor necrosis factor receptor(GITR)-triggered T_(Reg) suppression,remodeled the immunosuppressive network of tumor microenvironment.PLT-Bec1/DTA-1 promoted antigen presentation and T cell proliferation,and alleviated the low activity state of bone marrow-derived dendritic cells(BMDCs)in tumor suppressive environment.PLT-Bec1/DTA-1 inhibited tumor recurrence(5-and 13-fold lower of control group in tumor volume)and CD8^(+)T/T_(Reg) ratio(6.3-and 8.8-fold vs.control group)in mouse tumor model after intravenous or subcutaneous administration.Also,PLT-Bec1/DTA-1 prevented tumor colonization in lung through in situ immune activation,and was slightly superior to the combined of Bec1 and PD-L1.Our findings highlight the promise of delivering immunostimulatory payloads via bionic carriers,eliciting automatic in situ activation of effector immune cells in tumor microenvironment for tumor eradication.All these results provide promising prospects into the application of immunoactivator in improving cancer synergistic immunotherapy to overcome the bottlenecks in clinic.展开更多
Platelet microparticles(PMPs)are membrane particles derived from the platelet membrane that enter into the blood circulation.We sought to explore the therapeutic effects of Tao-Hong-Si-Wu Decoction(THSWD)on angiogenes...Platelet microparticles(PMPs)are membrane particles derived from the platelet membrane that enter into the blood circulation.We sought to explore the therapeutic effects of Tao-Hong-Si-Wu Decoction(THSWD)on angiogenesis in a rat model of cerebral ischaemia-reperfusion(I/R).The protective effect of THSWD on I/R rats was observed morphologically by immunohistochemical expression of VEGF and CD34,along with immunofluorescence results of co-expression of Brd U and v WF.Then,PMPs from different groups of rats were extracted,and cytokine array analysis was used to screen for angiogenesis associated proteins.The results showed that THSWD can promote the expression of VEGF,CD34,Brd U and v WF.Cytokine array analysis revealed the changes in the expression of 29 related angiogenic proteins in the total protein of PMPs,which involved the Notch signalling pathway.Compared with model group,the expression levels of NICD and Hes-1 in the THSWD group were significantly increased.In the context of I/R,the angiogenesis-related proteins of PMPs are different.THSWD may involve the promotion of activation of the Notch signalling pathway to achieve therapeutic effects on cerebral ischaemia.展开更多
Kawasaki disease(KD)is a medium vessel vasculitis with predilection to cause coronary artery abnormalities.KD is now the most common cause of acquired heart disease in developed countries.Thrombocytosis is consistentl...Kawasaki disease(KD)is a medium vessel vasculitis with predilection to cause coronary artery abnormalities.KD is now the most common cause of acquired heart disease in developed countries.Thrombocytosis is consistently found in patients with KD,usually in 2nd to 3rd week of illness.Thrombocytopenia has occasionally been reported in the acute phase of KD.An increase or decrease in platelet number in patients with KD was initially considered to be a benign phenomenon.However,recent literature on platelet biology in KD has suggested that platelets are not only increasing but are rather activated.This phenomenon has been found to increase the risk of thrombosis in these patients.Similarly a fall in platelet counts during acute stage of KD has also been found to be associated with increased severity of disease.In this review,we update on the current best understanding about pathogenic role of platelets in patients with KD.展开更多
基金We would like to thank the National Natural Science Foundation of China(No.81973258)the Beijing Natural Science Foundation(Nos.L202044,7202092)for funding this work.
文摘Immunotherapy has great promise in improving malignant tumor treatment.However,the efficacy of existing strategies is often limited by the immunosuppressive environment.Here,we demonstrate an in situ bionic immunoactivator,PLT-Bec1/DTA-1,with possessed natural advantages of platelets for tumor recruitment and activation,on which DTA-1(CD357 monoclonal antibody)and Bec1 were tethered as combined immune boosters.PLT-Bec1/DTA-1,as a self-triggered release repository,can deliver the pre-tethered Bec1 and DTA-1 deeply through the secretion of platelet microparticles(PMPs),thereby cooperate tacitly and exhibit superiority in immune activation of dendritic cells(DCs)and T cells via autophagy inducibility,coupled with glucocorticoid-induced tumor necrosis factor receptor(GITR)-triggered T_(Reg) suppression,remodeled the immunosuppressive network of tumor microenvironment.PLT-Bec1/DTA-1 promoted antigen presentation and T cell proliferation,and alleviated the low activity state of bone marrow-derived dendritic cells(BMDCs)in tumor suppressive environment.PLT-Bec1/DTA-1 inhibited tumor recurrence(5-and 13-fold lower of control group in tumor volume)and CD8^(+)T/T_(Reg) ratio(6.3-and 8.8-fold vs.control group)in mouse tumor model after intravenous or subcutaneous administration.Also,PLT-Bec1/DTA-1 prevented tumor colonization in lung through in situ immune activation,and was slightly superior to the combined of Bec1 and PD-L1.Our findings highlight the promise of delivering immunostimulatory payloads via bionic carriers,eliciting automatic in situ activation of effector immune cells in tumor microenvironment for tumor eradication.All these results provide promising prospects into the application of immunoactivator in improving cancer synergistic immunotherapy to overcome the bottlenecks in clinic.
基金supported by the National Natural Science Foundation of China(Nos.81473387 and 81503291)the Anhui Province Key Research and Development Program(No.1704a0802141)。
文摘Platelet microparticles(PMPs)are membrane particles derived from the platelet membrane that enter into the blood circulation.We sought to explore the therapeutic effects of Tao-Hong-Si-Wu Decoction(THSWD)on angiogenesis in a rat model of cerebral ischaemia-reperfusion(I/R).The protective effect of THSWD on I/R rats was observed morphologically by immunohistochemical expression of VEGF and CD34,along with immunofluorescence results of co-expression of Brd U and v WF.Then,PMPs from different groups of rats were extracted,and cytokine array analysis was used to screen for angiogenesis associated proteins.The results showed that THSWD can promote the expression of VEGF,CD34,Brd U and v WF.Cytokine array analysis revealed the changes in the expression of 29 related angiogenic proteins in the total protein of PMPs,which involved the Notch signalling pathway.Compared with model group,the expression levels of NICD and Hes-1 in the THSWD group were significantly increased.In the context of I/R,the angiogenesis-related proteins of PMPs are different.THSWD may involve the promotion of activation of the Notch signalling pathway to achieve therapeutic effects on cerebral ischaemia.
文摘Kawasaki disease(KD)is a medium vessel vasculitis with predilection to cause coronary artery abnormalities.KD is now the most common cause of acquired heart disease in developed countries.Thrombocytosis is consistently found in patients with KD,usually in 2nd to 3rd week of illness.Thrombocytopenia has occasionally been reported in the acute phase of KD.An increase or decrease in platelet number in patients with KD was initially considered to be a benign phenomenon.However,recent literature on platelet biology in KD has suggested that platelets are not only increasing but are rather activated.This phenomenon has been found to increase the risk of thrombosis in these patients.Similarly a fall in platelet counts during acute stage of KD has also been found to be associated with increased severity of disease.In this review,we update on the current best understanding about pathogenic role of platelets in patients with KD.
