Thermal ablation(TA),including radiofrequency ablation(RFA)and microwave ablation(MWA),has become the main treatment for early-stage hepatocellular carcinoma(HCC)due to advantages such as safety and minimal invasivene...Thermal ablation(TA),including radiofrequency ablation(RFA)and microwave ablation(MWA),has become the main treatment for early-stage hepatocellular carcinoma(HCC)due to advantages such as safety and minimal invasiveness.However,HCC is prone to local recurrence,with more aggressive malignancies after TA closely related to TA-induced changes in epithelial-mesenchymal transition(EMT)and remodeling of the tumor microenvironment(TME).According to many studies,various components of the TME undergo complex changes after TA,such as the recruitment of innate and adaptive immune cells,the release of tumor-associated antigens(TAAs)and various cytokines,the formation of a hypoxic microenvironment,and tumor angiogenesis.Changes in the TME after TA can partly enhance the anti-tumor immune response;however,this response is weak to kill the tumor completely.Certain components of the TME can induce an immunosuppressive microenvironment through complex interactions,leading to tumor recurrence and progression.How the TME is remodeled after TA and the mechanism by which the TME promotes HCC recurrence and progression are unclear.Thus,in this review,we focused on these issues to highlight potentially effective strategies for reducing and preventing the recurrence and progression of HCC after TA.展开更多
Thermal ablation(TA)as an effective method treating hepatocellular carcinoma(HCC)in clinics is facing great challenges of high recurrence and metastasis.Although immune-checkpoint blockade(ICB)-based immuno-therapy ha...Thermal ablation(TA)as an effective method treating hepatocellular carcinoma(HCC)in clinics is facing great challenges of high recurrence and metastasis.Although immune-checkpoint blockade(ICB)-based immuno-therapy has shown potential to inhibit recurrence and metastasis,the combination strategy of ICB and thermal ablation has shown little progress in HCC treatments.The tremendous hurdle for combining ICB with thermal ablation lies with the insufficient antigen internalization and immaturity of tumor-infiltrating dendritic cells(TIDCs)which leads to an inferior immune response to distant tumor growth and metastasis.Herein,an antigen-capturing nanoplatform,whose surface was modified with mannose as a targeting ligand,was constructed for co-delivering tumor-associated antigens(TAAs)and m6A demethylases inhibitor(i.e.,fat mass and obesity asso-ciated gene(FTO)inhibitor)into TIDCs.In vivo results demonstrate that the intratumoral injection of nanodrug followed by HCC thermal ablation promotes dendritic cells(DCs)maturation,improves tumor infiltration of effector T cells and generates immune memory,which synergize with ICB treatment to inhibit the distant tumor growth and lung metastasis.Therefore,the antigen-capturing and FTO-inhibiting nanodrug holds potential to boost the ICB-based immunotherapy against HCC after thermal ablation.展开更多
To the Editor:Portal vein tumor thrombus(PVTT)is present in 10%to 40%of patients with hepatocellular carcinoma(HCC)at diagnosis and has a profound adverse effect on progno-sis.[1]Sorafenib is recommended as the first-...To the Editor:Portal vein tumor thrombus(PVTT)is present in 10%to 40%of patients with hepatocellular carcinoma(HCC)at diagnosis and has a profound adverse effect on progno-sis.[1]Sorafenib is recommended as the first-line treatment for patients with advanced HCC,including those who have PVTT.However,its efficacy is modest.[1,2]A combination of transarterial chemoembolization(TACE)and sorafenib(TACE-S)has been reported to be associated with improved outcomes.[1,3]But unfortunately,its efficacy in controlling PVTT remained limited,with an objective response rate(ORR)of only 9.7%.[3]Previous studies have demonstrated that iodine-125(125I)seed brachytherapy targeting PVTT can lead to a significant reduction in tumor thrombus with few complications.[4,5]We hypothesized that TACE-S combined with 125I seed brachytherapy(TACE-S-I)could improve the control of PVTT and confer a greater survival benefit.Therefore,we conducted this study to evaluate the efficacy and safety of TACE-S-I compared with TACE-S in HCC patients with PVTT.This study was approved by our institutional review board(No.2020-hg-ks-03).展开更多
基金supported by National Natural Science Foundation of China(82001929,82172043)Basic and Applied Basic Research Foundation of Guangdong Province(2020A1515110654)
文摘Thermal ablation(TA),including radiofrequency ablation(RFA)and microwave ablation(MWA),has become the main treatment for early-stage hepatocellular carcinoma(HCC)due to advantages such as safety and minimal invasiveness.However,HCC is prone to local recurrence,with more aggressive malignancies after TA closely related to TA-induced changes in epithelial-mesenchymal transition(EMT)and remodeling of the tumor microenvironment(TME).According to many studies,various components of the TME undergo complex changes after TA,such as the recruitment of innate and adaptive immune cells,the release of tumor-associated antigens(TAAs)and various cytokines,the formation of a hypoxic microenvironment,and tumor angiogenesis.Changes in the TME after TA can partly enhance the anti-tumor immune response;however,this response is weak to kill the tumor completely.Certain components of the TME can induce an immunosuppressive microenvironment through complex interactions,leading to tumor recurrence and progression.How the TME is remodeled after TA and the mechanism by which the TME promotes HCC recurrence and progression are unclear.Thus,in this review,we focused on these issues to highlight potentially effective strategies for reducing and preventing the recurrence and progression of HCC after TA.
基金National Natural Science Foundation of China(51933011,31971296,52173125,82102194,81873920,82001930)Key Areas Research and Development Program of Guangzhou(202007020006)+2 种基金Natural Science Foundation of the Guangdong Province(2021A1515010250,2020A1515111206,2021A1515111006)China Postdoctoral Science Foundation(2020M680119,2021M703763)Funding of the Southern Medical University Nanfang Hospital(2019C015).
文摘Thermal ablation(TA)as an effective method treating hepatocellular carcinoma(HCC)in clinics is facing great challenges of high recurrence and metastasis.Although immune-checkpoint blockade(ICB)-based immuno-therapy has shown potential to inhibit recurrence and metastasis,the combination strategy of ICB and thermal ablation has shown little progress in HCC treatments.The tremendous hurdle for combining ICB with thermal ablation lies with the insufficient antigen internalization and immaturity of tumor-infiltrating dendritic cells(TIDCs)which leads to an inferior immune response to distant tumor growth and metastasis.Herein,an antigen-capturing nanoplatform,whose surface was modified with mannose as a targeting ligand,was constructed for co-delivering tumor-associated antigens(TAAs)and m6A demethylases inhibitor(i.e.,fat mass and obesity asso-ciated gene(FTO)inhibitor)into TIDCs.In vivo results demonstrate that the intratumoral injection of nanodrug followed by HCC thermal ablation promotes dendritic cells(DCs)maturation,improves tumor infiltration of effector T cells and generates immune memory,which synergize with ICB treatment to inhibit the distant tumor growth and lung metastasis.Therefore,the antigen-capturing and FTO-inhibiting nanodrug holds potential to boost the ICB-based immunotherapy against HCC after thermal ablation.
基金This work was supported by grants from the National Natural Science Foundation of China(Nos.81873920,81571774)the High-Level University Clinical Research Promotion Program of Guangzhou Medical University(No.B185004019)+1 种基金the Science and Technology Project of Guangzhou(No.202002030135)the Medical Science and Technology Research Foundation of Guangdong Province(Nos.A2019187,B2019055,and B2019089)。
文摘To the Editor:Portal vein tumor thrombus(PVTT)is present in 10%to 40%of patients with hepatocellular carcinoma(HCC)at diagnosis and has a profound adverse effect on progno-sis.[1]Sorafenib is recommended as the first-line treatment for patients with advanced HCC,including those who have PVTT.However,its efficacy is modest.[1,2]A combination of transarterial chemoembolization(TACE)and sorafenib(TACE-S)has been reported to be associated with improved outcomes.[1,3]But unfortunately,its efficacy in controlling PVTT remained limited,with an objective response rate(ORR)of only 9.7%.[3]Previous studies have demonstrated that iodine-125(125I)seed brachytherapy targeting PVTT can lead to a significant reduction in tumor thrombus with few complications.[4,5]We hypothesized that TACE-S combined with 125I seed brachytherapy(TACE-S-I)could improve the control of PVTT and confer a greater survival benefit.Therefore,we conducted this study to evaluate the efficacy and safety of TACE-S-I compared with TACE-S in HCC patients with PVTT.This study was approved by our institutional review board(No.2020-hg-ks-03).
