Intrahepatic cholangiocarcinoma(ICC)is the second most common liver cancer.Chemotherapy remains the main therapeutic strategy for advanced ICC patients,but chemosensitivity varies individually.Here,we applied cytometr...Intrahepatic cholangiocarcinoma(ICC)is the second most common liver cancer.Chemotherapy remains the main therapeutic strategy for advanced ICC patients,but chemosensitivity varies individually.Here,we applied cytometry by time-of-flight(CyTOF)to establish the immune profile of peripheral blood mononuclear cells(PBMCs)on the single-cell level at indicated time points before,during,and after chemotherapy.Multiplex immunofluorescence staining was applied to examine the spatial distribution of certain immune clusters.Tissue microarrays(TMAs)were used for prognostic evaluation.A total of 20 ICC patients treated with gemcitabine(GEM)were enrolled in our study,including eight cases with good response(R)and 12 cases with non-response(NR).Tremendous changes in PBMC composition,including an increased level of CD4/CD8 double-positive T cells(DPT),were observed after chemotherapy.Patients with higher level of CD4^(+)CD45RO^(+)CXCR3^(+)T cells before treatment had a favorable response to chemotherapy.Our study identified a positive correlation between the percentage of T cell subpopulations and clinical response after chemotherapy,which suggests that it is practical to predict the potential response before treatment by evaluating the proportions of the cell population in PBMCs.展开更多
On the global scale, hepatitis B virus(HBV) infection is the main cause of hepatocellular carcinoma(HCC) especially in regions of Asia where HBV infection is endemic. Epidemiological studies show that the incidence of...On the global scale, hepatitis B virus(HBV) infection is the main cause of hepatocellular carcinoma(HCC) especially in regions of Asia where HBV infection is endemic. Epidemiological studies show that the incidence of inflammation-driven HCC in males is three times as high as in females. Recent studies suggest that sex hormones have a crucial role in the pathogenesis and development of HBV-induced HCC. We found that the estrogen/androgen signaling pathway is associated with decreased/increased transcription and replication of HBV genes and can promote the development of HBV infections by up/downregulating HBV RNA transcription and inflammatory cytokines levels, which in turn slow down the progression of HBV-induced HCC. Additionally, sex hormones can also affect HBV-related HCC by inducing epigenetic changes. The evidence that both morphology and function of the human liver are affected by sex hormones was found over 60 years ago. However,the underlying molecular mechanism largely remains to be elucidated. This review focuses mainly on the molecular mechanisms behind the sex difference in HCC associated with HBV and other factors. In addition, several potential treatment and therapeutic strategies for inflammation-driven HCC will be introduced in this review.展开更多
基金This work was supported by the National Research Program of China(2017YFA0505803 and 2017YFC0908100)the State Key Project for Infectious Diseases(2018ZX10732202-001)+2 种基金National Natural Science Foundation of China(81790633,81672860,61922047,81422032,and 81902412)National Natural Science Foundation of Shanghai,China(17ZR143800)National Science Foundation for Distinguished Young Scholars of China(81702298).
文摘Intrahepatic cholangiocarcinoma(ICC)is the second most common liver cancer.Chemotherapy remains the main therapeutic strategy for advanced ICC patients,but chemosensitivity varies individually.Here,we applied cytometry by time-of-flight(CyTOF)to establish the immune profile of peripheral blood mononuclear cells(PBMCs)on the single-cell level at indicated time points before,during,and after chemotherapy.Multiplex immunofluorescence staining was applied to examine the spatial distribution of certain immune clusters.Tissue microarrays(TMAs)were used for prognostic evaluation.A total of 20 ICC patients treated with gemcitabine(GEM)were enrolled in our study,including eight cases with good response(R)and 12 cases with non-response(NR).Tremendous changes in PBMC composition,including an increased level of CD4/CD8 double-positive T cells(DPT),were observed after chemotherapy.Patients with higher level of CD4^(+)CD45RO^(+)CXCR3^(+)T cells before treatment had a favorable response to chemotherapy.Our study identified a positive correlation between the percentage of T cell subpopulations and clinical response after chemotherapy,which suggests that it is practical to predict the potential response before treatment by evaluating the proportions of the cell population in PBMCs.
基金supported by the State Key Project for Liver Cancer(2012ZX10002009)National Natural Science Foundation of China(81301811,81521091,81422032,81272212,81672860,81372674,and 91529303)+1 种基金Science Foundation of Shanghai(134119a3700)Strategic Priority Research Program of the Chinese Academy of Sciences(XDA12010201)
文摘On the global scale, hepatitis B virus(HBV) infection is the main cause of hepatocellular carcinoma(HCC) especially in regions of Asia where HBV infection is endemic. Epidemiological studies show that the incidence of inflammation-driven HCC in males is three times as high as in females. Recent studies suggest that sex hormones have a crucial role in the pathogenesis and development of HBV-induced HCC. We found that the estrogen/androgen signaling pathway is associated with decreased/increased transcription and replication of HBV genes and can promote the development of HBV infections by up/downregulating HBV RNA transcription and inflammatory cytokines levels, which in turn slow down the progression of HBV-induced HCC. Additionally, sex hormones can also affect HBV-related HCC by inducing epigenetic changes. The evidence that both morphology and function of the human liver are affected by sex hormones was found over 60 years ago. However,the underlying molecular mechanism largely remains to be elucidated. This review focuses mainly on the molecular mechanisms behind the sex difference in HCC associated with HBV and other factors. In addition, several potential treatment and therapeutic strategies for inflammation-driven HCC will be introduced in this review.
