Cancer immunotherapy has emerged as a promising strategy for the treatment of cancer,with the tumor microenvironment(TME)playing a pivotal role in modulating the immune response.CD47,a cell surface protein,has been id...Cancer immunotherapy has emerged as a promising strategy for the treatment of cancer,with the tumor microenvironment(TME)playing a pivotal role in modulating the immune response.CD47,a cell surface protein,has been identified as a crucial regulator of the TME and a potential therapeutic target for cancer therapy.However,the precise functions and implications of CD47 in the TME during immunotherapy for cancer patients remain incompletely understood.This comprehensive review aims to provide an overview of CD47’s multifaced role in TME regulation and immune evasion,elucidating its impact on various types of immunotherapy outcomes,including checkpoint inhibitors and CAR T-cell therapy.Notably,CD47-targeted therapies offer a promising avenue for improving cancer treatment outcomes,especially when combined with other immunotherapeutic approaches.The review also discusses current and potential CD47-targeted therapies being explored for cancer treatment and delves into the associated challenges and opportunities inherent in targeting CD47.Despite the demonstrated effectiveness of CD47-targeted therapies,there are potential problems,including unintended effects on healthy cells,hematological toxicities,and the development if resistance.Consequently,further research efforts are warranted to fully understand the underlying mechanisms of resistance and to optimize CD47-targeted therapies through innovative combination approaches,ultimately improving cancer treatment outcomes.Overall,this comprehensive review highlights the significance of CD47 as a promising target for cancer immunotherapy and provides valuable insight into the challenges and opportunities in developing effective CD47-targeted therapies for cancer treatment.展开更多
Osteosarcoma is a malignant tumor originating from bone tissue that progresses rapidly and has a poor patient prognosis.Immunotherapy has shown great potential in the treatment of osteosarcoma.However,the immunosuppre...Osteosarcoma is a malignant tumor originating from bone tissue that progresses rapidly and has a poor patient prognosis.Immunotherapy has shown great potential in the treatment of osteosarcoma.However,the immunosuppressive microenvironment severely limits the efficacy of osteosarcoma treatment.The dual pH-sensitive nanocarrier has emerged as an effective antitumor drug delivery system that can selectively release drugs into the acidic tumor microenvironment.Here,we prepared a dual pH-sensitive nanocarrier,loaded with the photosensitizer Chlorin e6(Ce6)and CD47 monoclonal antibodies(aCD47),to deliver synergistic photodynamic and immunotherapy of osteosarcoma.On laser irradiation,Ce6 can generate reactive oxygen species(ROS)to kill cancer cells directly and induces immunogenic tumor cell death(ICD),which further facilitates the dendritic cell maturation induced by blockade of CD47 by aCD47.Moreover,both calreticulin released during ICD and CD47 blockade can accelerate phagocytosis of tumor cells by macrophages,promote antigen presentation,and eventually induce T lymphocyte-mediated antitumor immunity.Overall,the dual pH-sensitive nanodrug loaded with Ce6 and aCD47 showed excellent immune-activating and anti-tumor effects in osteosarcoma,which may lay the theoretical foundation for a novel combination model of osteosarcoma treatment.展开更多
Background:The specific impact of sphingolipid metabolism on developing hepatocellular Carcinoma(HCC)remains unclear.This study aims to explore the relationship between sphingolipid metabolism and HCC prognosis,immune ...Background:The specific impact of sphingolipid metabolism on developing hepatocellular Carcinoma(HCC)remains unclear.This study aims to explore the relationship between sphingolipid metabolism and HCC prognosis,immune response,and drug sensitivity.Methods:Data were obtained from The Cancer Genome Atlas(TCGA)-Hepatocellular Carcinoma(LIHC)and Gene Expression Omnibus(GEO,GSE14520 datasets).47 sphingolipid metabolism genes were obtained from the Kyoto Encyclopedia of Genes and Genomes(KEGG)database.After classifying HCC samples using the Non-negative Matrix Factorization(NMF)clustering method,differentially expressed genes were screened.Then,8 risk genes were obtained by univariate analysis,survival random forest reduction and lasso analysis.The expression of 8 risk genes was verified in vitro.Results:8 risk genes were used to construct the Sphingolipid score model.High-Sphingolipid score predicted poor prognosis of HCC patients.Sphingolipid score was associated with immune checkpoints(IL-1B,TLR4,TGFB1,and IL-10),immune cells(Th2,Treg,MDSC,Neutrophil,Fibroblasts and macrophage),and MAPK Cascade.In the High-Sphingolipid score group,a significantly higher proportion of patients with TP53(p53)mutations was significantly higher(56%).Furthermore,patients with a high-Sphingolipid score were predicted to have a higher sensitivity to chemotherapy drugs.In vitro validation showed that compared with normal liver cells LX-2,TRIM47,and S100A9 significantly increased in liver cancer cells Hep G2,MHCC-97H,and Hep3B2.1-7,while SLC1A7,LPCAT1,and CFHR4 significantly decreased.Silencing TRIM47 reduced the proliferation and promoted apoptosis.The levels of ceramide synthesis-related indexes(CERS1,CERS6,CERS5,and SPTLC2)increased,and the ACER3 related to catalytic hydrolysis decreased.Conclusion:We constructed a sphingolipid metabolism-related prognostic signature(Sphingolipid score)based on 8 risk genes.TRIM47 may affect the development of liver cancer by regulating the relevant indicators of ceramide synthesis and catalytic hydrolysis.展开更多
Objective:To explore the regulatory mechanism of NUDT5 in glioblastoma multiforme(GBM).Methods:GEPIA database was used to predict the expressions of NUDT5 and tripartite motif family proteins 47(TRIM47)in GBM patients...Objective:To explore the regulatory mechanism of NUDT5 in glioblastoma multiforme(GBM).Methods:GEPIA database was used to predict the expressions of NUDT5 and tripartite motif family proteins 47(TRIM47)in GBM patients.RT-qPCR and Western blot analyses were performed to examine NUDT5 expression in GBM cells.LN-229 cell proliferation,migration as well as invasion were estimated by CCK-8,colony formation,wound healing,and Transwell assays following interference with NUDT5.ECAR assay,L-lactic acid kit,glucose detection kit,and ATP detection kit were applied for the detection of glycolysis-related indexes.Co-immunoprecipitation experiment was carried out to verify the relationship between NUDT5 and TRIM47.Results:GEPIA database showed that NUDT5 expression was significantly increased in GBM patients.Inhibiting the expression of NUDT5 in GBM cells significantly suppressed the viability,proliferation,invasion,migration,and glycolysis of GBM cells.Moreover,TRIM47 was highly expressed in GBM cells and interacted with NUDT5.Overexpression of TRIM47 partially reversed the inhibitory effect of NUDT5 downregulation on the proliferation,metastasis,and glycolysis of GBM cells.Conclusions:NUDT5 promotes the growth,metastasis,and Warburg effect of GBM cells by upregulating TRIM47.Both NUDT5 and TRIM47 can be used as targets for GMB treatment.展开更多
Long noncoding RNA(lncRNA)IDH1 antisense RNA 1(IDH1-AS1)is involved in the progression of multiple cancers,but its role in epithelial ovarian cancer(EOC)is unknown.Therefore,we investigated the expression levels of ID...Long noncoding RNA(lncRNA)IDH1 antisense RNA 1(IDH1-AS1)is involved in the progression of multiple cancers,but its role in epithelial ovarian cancer(EOC)is unknown.Therefore,we investigated the expression levels of IDH1-AS1 in EOC cells and normal ovarian epithelial cells by quantitative real-time PCR(qPCR).We first evaluated the effects of IDH1-AS1 on the proliferation,migration,and invasion of EOC cells through cell counting kit-8,colony formation,EdU,transwell,wound-healing,and xenograft assays.We then explored the downstream targets of IDH1-AS1 and verified the results by a dual-luciferase reporter,qPCR,rescue experiments,and Western blotting.We found that the expression levels of IDH1-AS1 were lower in EOC cells than in normal ovarian epithelial cells.High IDH1-AS1 expression of EOC patients from the Gene Expression Profiling Interactive Analysis database indicated a favorable prognosis,because IDH1-AS1 inhibited cell proliferation and xenograft tumor growth of EOC.IDH1-AS1 sponged miR-518c-5p whose overexpression promoted EOC cell proliferation.The miR-518c-5p mimic also reversed the proliferation-inhibiting effect induced by IDH1-AS1 overexpression.Furthermore,we found that RNA binding motif protein 47(RBM47)was the downstream target of miR-518c-5p,that upregulation of RBM47 inhibited EOC cell proliferation,and that RBM47 overexpressing plasmid counteracted the proliferation-promoting effect caused by the IDH1-AS1 knockdown.Taken together,IDH1-AS1 may suppress EOC cell proliferation and tumor growth via the miR-518c-5p/RBM47 axis.展开更多
基金the Huzhou Science and Technology Bureau,Zhejiang Province,China(2020GZ41).
文摘Cancer immunotherapy has emerged as a promising strategy for the treatment of cancer,with the tumor microenvironment(TME)playing a pivotal role in modulating the immune response.CD47,a cell surface protein,has been identified as a crucial regulator of the TME and a potential therapeutic target for cancer therapy.However,the precise functions and implications of CD47 in the TME during immunotherapy for cancer patients remain incompletely understood.This comprehensive review aims to provide an overview of CD47’s multifaced role in TME regulation and immune evasion,elucidating its impact on various types of immunotherapy outcomes,including checkpoint inhibitors and CAR T-cell therapy.Notably,CD47-targeted therapies offer a promising avenue for improving cancer treatment outcomes,especially when combined with other immunotherapeutic approaches.The review also discusses current and potential CD47-targeted therapies being explored for cancer treatment and delves into the associated challenges and opportunities inherent in targeting CD47.Despite the demonstrated effectiveness of CD47-targeted therapies,there are potential problems,including unintended effects on healthy cells,hematological toxicities,and the development if resistance.Consequently,further research efforts are warranted to fully understand the underlying mechanisms of resistance and to optimize CD47-targeted therapies through innovative combination approaches,ultimately improving cancer treatment outcomes.Overall,this comprehensive review highlights the significance of CD47 as a promising target for cancer immunotherapy and provides valuable insight into the challenges and opportunities in developing effective CD47-targeted therapies for cancer treatment.
文摘Osteosarcoma is a malignant tumor originating from bone tissue that progresses rapidly and has a poor patient prognosis.Immunotherapy has shown great potential in the treatment of osteosarcoma.However,the immunosuppressive microenvironment severely limits the efficacy of osteosarcoma treatment.The dual pH-sensitive nanocarrier has emerged as an effective antitumor drug delivery system that can selectively release drugs into the acidic tumor microenvironment.Here,we prepared a dual pH-sensitive nanocarrier,loaded with the photosensitizer Chlorin e6(Ce6)and CD47 monoclonal antibodies(aCD47),to deliver synergistic photodynamic and immunotherapy of osteosarcoma.On laser irradiation,Ce6 can generate reactive oxygen species(ROS)to kill cancer cells directly and induces immunogenic tumor cell death(ICD),which further facilitates the dendritic cell maturation induced by blockade of CD47 by aCD47.Moreover,both calreticulin released during ICD and CD47 blockade can accelerate phagocytosis of tumor cells by macrophages,promote antigen presentation,and eventually induce T lymphocyte-mediated antitumor immunity.Overall,the dual pH-sensitive nanodrug loaded with Ce6 and aCD47 showed excellent immune-activating and anti-tumor effects in osteosarcoma,which may lay the theoretical foundation for a novel combination model of osteosarcoma treatment.
基金The work was supported by funds from The Science and Technology Project of Hangzhou City(Agriculture and Social Development,No.2016007)&(Agriculture and Social Development,No.20201231Y131)&(Social Development,No.20140633B57)The Science and Technology Project of Yuhang District,Hangzhou City(Nos.2017002&2014003)+2 种基金The Health Science and Technology Project of Hangzhou City(No.2015B32)Zhejiang Provincial Natural Science Foundation of China under Grant(No.LTGY23H160006)The Health Science and Technology Project of Zhejiang Province(No.2023XY009).
文摘Background:The specific impact of sphingolipid metabolism on developing hepatocellular Carcinoma(HCC)remains unclear.This study aims to explore the relationship between sphingolipid metabolism and HCC prognosis,immune response,and drug sensitivity.Methods:Data were obtained from The Cancer Genome Atlas(TCGA)-Hepatocellular Carcinoma(LIHC)and Gene Expression Omnibus(GEO,GSE14520 datasets).47 sphingolipid metabolism genes were obtained from the Kyoto Encyclopedia of Genes and Genomes(KEGG)database.After classifying HCC samples using the Non-negative Matrix Factorization(NMF)clustering method,differentially expressed genes were screened.Then,8 risk genes were obtained by univariate analysis,survival random forest reduction and lasso analysis.The expression of 8 risk genes was verified in vitro.Results:8 risk genes were used to construct the Sphingolipid score model.High-Sphingolipid score predicted poor prognosis of HCC patients.Sphingolipid score was associated with immune checkpoints(IL-1B,TLR4,TGFB1,and IL-10),immune cells(Th2,Treg,MDSC,Neutrophil,Fibroblasts and macrophage),and MAPK Cascade.In the High-Sphingolipid score group,a significantly higher proportion of patients with TP53(p53)mutations was significantly higher(56%).Furthermore,patients with a high-Sphingolipid score were predicted to have a higher sensitivity to chemotherapy drugs.In vitro validation showed that compared with normal liver cells LX-2,TRIM47,and S100A9 significantly increased in liver cancer cells Hep G2,MHCC-97H,and Hep3B2.1-7,while SLC1A7,LPCAT1,and CFHR4 significantly decreased.Silencing TRIM47 reduced the proliferation and promoted apoptosis.The levels of ceramide synthesis-related indexes(CERS1,CERS6,CERS5,and SPTLC2)increased,and the ACER3 related to catalytic hydrolysis decreased.Conclusion:We constructed a sphingolipid metabolism-related prognostic signature(Sphingolipid score)based on 8 risk genes.TRIM47 may affect the development of liver cancer by regulating the relevant indicators of ceramide synthesis and catalytic hydrolysis.
文摘Objective:To explore the regulatory mechanism of NUDT5 in glioblastoma multiforme(GBM).Methods:GEPIA database was used to predict the expressions of NUDT5 and tripartite motif family proteins 47(TRIM47)in GBM patients.RT-qPCR and Western blot analyses were performed to examine NUDT5 expression in GBM cells.LN-229 cell proliferation,migration as well as invasion were estimated by CCK-8,colony formation,wound healing,and Transwell assays following interference with NUDT5.ECAR assay,L-lactic acid kit,glucose detection kit,and ATP detection kit were applied for the detection of glycolysis-related indexes.Co-immunoprecipitation experiment was carried out to verify the relationship between NUDT5 and TRIM47.Results:GEPIA database showed that NUDT5 expression was significantly increased in GBM patients.Inhibiting the expression of NUDT5 in GBM cells significantly suppressed the viability,proliferation,invasion,migration,and glycolysis of GBM cells.Moreover,TRIM47 was highly expressed in GBM cells and interacted with NUDT5.Overexpression of TRIM47 partially reversed the inhibitory effect of NUDT5 downregulation on the proliferation,metastasis,and glycolysis of GBM cells.Conclusions:NUDT5 promotes the growth,metastasis,and Warburg effect of GBM cells by upregulating TRIM47.Both NUDT5 and TRIM47 can be used as targets for GMB treatment.
基金supported by the National Natural Science Foundation of China(Grant Nos.81572556 and 81402139).
文摘Long noncoding RNA(lncRNA)IDH1 antisense RNA 1(IDH1-AS1)is involved in the progression of multiple cancers,but its role in epithelial ovarian cancer(EOC)is unknown.Therefore,we investigated the expression levels of IDH1-AS1 in EOC cells and normal ovarian epithelial cells by quantitative real-time PCR(qPCR).We first evaluated the effects of IDH1-AS1 on the proliferation,migration,and invasion of EOC cells through cell counting kit-8,colony formation,EdU,transwell,wound-healing,and xenograft assays.We then explored the downstream targets of IDH1-AS1 and verified the results by a dual-luciferase reporter,qPCR,rescue experiments,and Western blotting.We found that the expression levels of IDH1-AS1 were lower in EOC cells than in normal ovarian epithelial cells.High IDH1-AS1 expression of EOC patients from the Gene Expression Profiling Interactive Analysis database indicated a favorable prognosis,because IDH1-AS1 inhibited cell proliferation and xenograft tumor growth of EOC.IDH1-AS1 sponged miR-518c-5p whose overexpression promoted EOC cell proliferation.The miR-518c-5p mimic also reversed the proliferation-inhibiting effect induced by IDH1-AS1 overexpression.Furthermore,we found that RNA binding motif protein 47(RBM47)was the downstream target of miR-518c-5p,that upregulation of RBM47 inhibited EOC cell proliferation,and that RBM47 overexpressing plasmid counteracted the proliferation-promoting effect caused by the IDH1-AS1 knockdown.Taken together,IDH1-AS1 may suppress EOC cell proliferation and tumor growth via the miR-518c-5p/RBM47 axis.
