BACKGROUND Colony-stimulating factor 3(CSF3)and its receptor(CSF3R)are known to promote gastric cancer(GC)growth and metastasis.However,their effects on the immune microenvironment remain unclear.Our analysis indicate...BACKGROUND Colony-stimulating factor 3(CSF3)and its receptor(CSF3R)are known to promote gastric cancer(GC)growth and metastasis.However,their effects on the immune microenvironment remain unclear.Our analysis indicated a potential link between CSF3R expression and the immunosuppressive receptor leukocyte immunoglobulin-like receptor B2(LILRB2)in GC.We hypothesized that CSF3/CSF3R may regulate LILRB2 and its ligands,angiopoietin-like protein 2(ANGPTL2)and human leukocyte antigen-G(HLA-G),contributing to immunosuppression.AIM To investigate the relationship between CSF3/CSF3R and LILRB2,as well as its ligands ANGPTL2 and HLA-G,in GC.METHODS Transcriptome sequencing data from The Cancer Genome Atlas were analyzed,stratifying patients by CSF3R expression.Differentially expressed genes and immune checkpoints were evaluated.Immunohistochemistry(IHC)was performed on GC tissues.Correlation analyses of CSF3R,LILRB2,ANGPTL2,and HLA-G were conducted using The Cancer Genome Atlas data and IHC results.GC cells were treated with CSF3,and expression levels of LILRB2,ANGPTL2,and HLA-G were measured by quantitative reverse transcriptase-polymerase chain reaction and western blotting.RESULTS Among 122 upregulated genes in high CSF3R expression groups,LILRB2 showed the most significant increase.IHC results indicated high expression of LILRB2(63.0%),ANGPTL2(56.5%),and HLA-G(73.9%)in GC tissues.Strong positive correlations existed between CSF3R and LILRB2,ANGPTL2,and HLA-G mRNA levels(P<0.001).IHC confirmed positive correlations between CSF3R and LILRB2(P<0.001),and HLA-G(P=0.010),but not ANGPTL2(P>0.05).CSF3 increased LILRB2,ANGPTL2,and HLA-G expression in GC cells.Heterogeneous nuclear ribonucleoprotein H1 modulation significantly altered their expression,impacting CSF3’s regulatory effects.CONCLUSION The CSF3/CSF3R pathway may contribute to immunosuppression in GC by upregulating LILRB2 and its ligands,with heterogeneous nuclear ribonucleoprotein H1 playing a regulatory role.展开更多
Colorectal cancer (CRC) is one of the most diffuse cancers worldwide and is still a clinical burden. Increasing evidences associate CRC clinical outcome to immune contexture represented by adaptive immune cells. Their...Colorectal cancer (CRC) is one of the most diffuse cancers worldwide and is still a clinical burden. Increasing evidences associate CRC clinical outcome to immune contexture represented by adaptive immune cells. Their type, density and location are summarized in the Immune Score that has been shown to improve prognostic prediction of CRC patients. The non-classical MHC class I human leukocyte antigen-G (HLA-G), is a crucial tumor-driven immune escape molecule involved in immune tolerance. HLA-G and soluble counterparts are able to exert inhibitory functions by direct interactions with inhibitory receptors present on both innate cells such as natural killer cells, and adaptive immune cells as cytotoxic T and B lymphocytes. HLA-G may play a prominent role in CRC strategies to avoid host immunosurveillance. This review highlights the current knowledge on HLA-G contribution in CRC, in related inflammatory diseases and in other type of cancers and disorders. HLA-G genetic setting (specific haplotypes, genotypes and alleles frequencies) and association with circulating/soluble profiles was highlighted. HLA G prognostic and predictive value in CRC was investigated in order to define a novel prognostic immune biomarker in CRC.展开更多
Human leukocyte antigen-G(HLA-G) is a non-classical HLA class Ⅰ molecule that differs from classical HLA class Ⅰ molecules by low polymorphism and tissue distribution. HLA-G is a tolerogenic molecule with an immune-...Human leukocyte antigen-G(HLA-G) is a non-classical HLA class Ⅰ molecule that differs from classical HLA class Ⅰ molecules by low polymorphism and tissue distribution. HLA-G is a tolerogenic molecule with an immune-modulatory and anti-inflammatory function on both innate and adaptative immunity. This peculiar characteristic of HLA-G has led to investigations of its role in pathological conditions in order to define possible uses in diagnosis, prevention and treatment. In recent years, HLA-G has been shown to have an important implication in different inflammatory and autoimmune diseases, pregnancy complications, tumor development and aggressiveness, and susceptibility to viral infections. In fact, HLA-G molecules have been reported to alternate at both genetic and protein level in different disease situations, supporting its crucial role in pathological conditions. Specific pathologies show altered levels of soluble(s)HLA-G and different HLA-G gene polymorphisms seem to correlate with disease. This review aims to update scientific knowledge on the contribution of HLA-G in managing pathological conditions.展开更多
Objective:To explore the correlation between the distribution of 14bp polymorphism in exon 8 of human leukocyte antigen-G(HLA-G)gene in Hainan Li nationality and susceptibility to severe preeclampsia.Methods:100 cases...Objective:To explore the correlation between the distribution of 14bp polymorphism in exon 8 of human leukocyte antigen-G(HLA-G)gene in Hainan Li nationality and susceptibility to severe preeclampsia.Methods:100 cases of severe preeclampsia inpatients(experimental group)admitted to our hospital from June 2018 to September 2019 were selected.Among them,50 were Li and 50 were Han,and 100 were admitted to our hospital during the same period Normal pregnant women were the control group,including 50 cases of Li nationality and 50 cases of Han nationality.Venous blood was collected to detect the 14bp polymorphism in HLA-G gene exon 8,and the correlation between the 14bp polymorphism in HLA-G gene exon 8 and susceptibility to severe preeclampsia was analyzed.Results:There was a statistically significant difference in the 14-bp genotyping and allele frequency in HLA-G exon 8 of the Li ethnic group in the control group and the experimental group(P<0.05).The SBP and DBP of the Li 14-14/14bp typing,+14bp/-14bp typing,and allele-14bp typing were lower in the experimental group than in the Han group in the experimental group(P<0.05),and the SBP of+14bp/-14bp typing DBP was higher than that of Han patients in the experimental group(P<0.05).Binary Logistic Regression Analysis+14bp/-14bp was associated with the incidence of severe preeclampsia in Li women in Hainan region(P<0.05).The-14bp/-14bp classification was a protective factor for severe preeclampsia in Li women in Hainan region(P<0.05).Conclusion:The HLA-G gene exon 8 carrying a 14bp deletion polymorphism in the Hainan Li nationality is associated with preeclampsia susceptibility and progression.展开更多
基金Supported by Hebei Province Medical Science Research Project Plan,No.20230755.
文摘BACKGROUND Colony-stimulating factor 3(CSF3)and its receptor(CSF3R)are known to promote gastric cancer(GC)growth and metastasis.However,their effects on the immune microenvironment remain unclear.Our analysis indicated a potential link between CSF3R expression and the immunosuppressive receptor leukocyte immunoglobulin-like receptor B2(LILRB2)in GC.We hypothesized that CSF3/CSF3R may regulate LILRB2 and its ligands,angiopoietin-like protein 2(ANGPTL2)and human leukocyte antigen-G(HLA-G),contributing to immunosuppression.AIM To investigate the relationship between CSF3/CSF3R and LILRB2,as well as its ligands ANGPTL2 and HLA-G,in GC.METHODS Transcriptome sequencing data from The Cancer Genome Atlas were analyzed,stratifying patients by CSF3R expression.Differentially expressed genes and immune checkpoints were evaluated.Immunohistochemistry(IHC)was performed on GC tissues.Correlation analyses of CSF3R,LILRB2,ANGPTL2,and HLA-G were conducted using The Cancer Genome Atlas data and IHC results.GC cells were treated with CSF3,and expression levels of LILRB2,ANGPTL2,and HLA-G were measured by quantitative reverse transcriptase-polymerase chain reaction and western blotting.RESULTS Among 122 upregulated genes in high CSF3R expression groups,LILRB2 showed the most significant increase.IHC results indicated high expression of LILRB2(63.0%),ANGPTL2(56.5%),and HLA-G(73.9%)in GC tissues.Strong positive correlations existed between CSF3R and LILRB2,ANGPTL2,and HLA-G mRNA levels(P<0.001).IHC confirmed positive correlations between CSF3R and LILRB2(P<0.001),and HLA-G(P=0.010),but not ANGPTL2(P>0.05).CSF3 increased LILRB2,ANGPTL2,and HLA-G expression in GC cells.Heterogeneous nuclear ribonucleoprotein H1 modulation significantly altered their expression,impacting CSF3’s regulatory effects.CONCLUSION The CSF3/CSF3R pathway may contribute to immunosuppression in GC by upregulating LILRB2 and its ligands,with heterogeneous nuclear ribonucleoprotein H1 playing a regulatory role.
基金Supported by Associazione Italiana per la Ricerca sul Cancro(AIRC),Special Program Molecular Clinical Oncology,5X1000,No.12214(G.T.)European Research Council,Programme‘‘Ide-as’’,Proposal No.269051(G.T.,F.R.)
文摘Colorectal cancer (CRC) is one of the most diffuse cancers worldwide and is still a clinical burden. Increasing evidences associate CRC clinical outcome to immune contexture represented by adaptive immune cells. Their type, density and location are summarized in the Immune Score that has been shown to improve prognostic prediction of CRC patients. The non-classical MHC class I human leukocyte antigen-G (HLA-G), is a crucial tumor-driven immune escape molecule involved in immune tolerance. HLA-G and soluble counterparts are able to exert inhibitory functions by direct interactions with inhibitory receptors present on both innate cells such as natural killer cells, and adaptive immune cells as cytotoxic T and B lymphocytes. HLA-G may play a prominent role in CRC strategies to avoid host immunosurveillance. This review highlights the current knowledge on HLA-G contribution in CRC, in related inflammatory diseases and in other type of cancers and disorders. HLA-G genetic setting (specific haplotypes, genotypes and alleles frequencies) and association with circulating/soluble profiles was highlighted. HLA G prognostic and predictive value in CRC was investigated in order to define a novel prognostic immune biomarker in CRC.
文摘Human leukocyte antigen-G(HLA-G) is a non-classical HLA class Ⅰ molecule that differs from classical HLA class Ⅰ molecules by low polymorphism and tissue distribution. HLA-G is a tolerogenic molecule with an immune-modulatory and anti-inflammatory function on both innate and adaptative immunity. This peculiar characteristic of HLA-G has led to investigations of its role in pathological conditions in order to define possible uses in diagnosis, prevention and treatment. In recent years, HLA-G has been shown to have an important implication in different inflammatory and autoimmune diseases, pregnancy complications, tumor development and aggressiveness, and susceptibility to viral infections. In fact, HLA-G molecules have been reported to alternate at both genetic and protein level in different disease situations, supporting its crucial role in pathological conditions. Specific pathologies show altered levels of soluble(s)HLA-G and different HLA-G gene polymorphisms seem to correlate with disease. This review aims to update scientific knowledge on the contribution of HLA-G in managing pathological conditions.
基金Medical and health research project of Hainan Provincial(1901031027A2001)
文摘Objective:To explore the correlation between the distribution of 14bp polymorphism in exon 8 of human leukocyte antigen-G(HLA-G)gene in Hainan Li nationality and susceptibility to severe preeclampsia.Methods:100 cases of severe preeclampsia inpatients(experimental group)admitted to our hospital from June 2018 to September 2019 were selected.Among them,50 were Li and 50 were Han,and 100 were admitted to our hospital during the same period Normal pregnant women were the control group,including 50 cases of Li nationality and 50 cases of Han nationality.Venous blood was collected to detect the 14bp polymorphism in HLA-G gene exon 8,and the correlation between the 14bp polymorphism in HLA-G gene exon 8 and susceptibility to severe preeclampsia was analyzed.Results:There was a statistically significant difference in the 14-bp genotyping and allele frequency in HLA-G exon 8 of the Li ethnic group in the control group and the experimental group(P<0.05).The SBP and DBP of the Li 14-14/14bp typing,+14bp/-14bp typing,and allele-14bp typing were lower in the experimental group than in the Han group in the experimental group(P<0.05),and the SBP of+14bp/-14bp typing DBP was higher than that of Han patients in the experimental group(P<0.05).Binary Logistic Regression Analysis+14bp/-14bp was associated with the incidence of severe preeclampsia in Li women in Hainan region(P<0.05).The-14bp/-14bp classification was a protective factor for severe preeclampsia in Li women in Hainan region(P<0.05).Conclusion:The HLA-G gene exon 8 carrying a 14bp deletion polymorphism in the Hainan Li nationality is associated with preeclampsia susceptibility and progression.
