Primary cutaneous gamma-delta T-cell lymphoma (PCGD-TCL) is a very uncommon and extremely aggressive tumor, and is described in the newly re-vised World health organization for research and treatment of cancer classif...Primary cutaneous gamma-delta T-cell lymphoma (PCGD-TCL) is a very uncommon and extremely aggressive tumor, and is described in the newly re-vised World health organization for research and treatment of cancer classification of cutaneous lymphomas. A 43-year-old male patient presented with a 4 months history of cutaneous lesion over upper lip, without plaque and any constitutional symptom. Histopathological examination of skin biopsy revealed infiltration of atypical lymphocytes with hyperchromatic irregular nuclei. Immunophenotyping pattern of skin biopsy was compatible with PCGD-TLC. It is a highly aggressive tumor resistant to chemotherapy, immunotherapy, and radiation therapy. The GDTCL is characterized by a worse prognosis with a median survival of 15 months. Early diagnosis is essential and aggressive therapy is necessary.展开更多
Conventional adaptive T cell responses contribute to liver inflammation and fibrogenesis,especially in chronic viral infections and autoimmune hepatitis.However,the role of unconventional gamma-delta(γδ)T cells in l...Conventional adaptive T cell responses contribute to liver inflammation and fibrogenesis,especially in chronic viral infections and autoimmune hepatitis.However,the role of unconventional gamma-delta(γδ)T cells in liver diseases is less clear.In the past two decades,accumulating evidence revealed thatγδT cell numbers remarkably increase in the liver upon various inflammatory conditions in mice and humans.More recent studies demonstrated that the functional effect ofγδT cells on liver disease progression depends on the subsets involved,which can be identified by the expression of distinct T cell receptor chains and of specific cytokines.Fascinatingly,γδT cells may have protective as well as pathogenic functions in liver diseases.Interferonγ-producingγδT cells,for example,induce apoptosis in hepatocytes but also in hepatic tumor cells;while interleukin-17-expressingγδT cells can downregulate pathogenic effector functions of other immune cells and can promote apoptosis of fibrogenic stellate cells.However,the results obtained in human liver disease as well as murine models are not fully conclusive at present,and the effects ofγδT cells on the outcome of liver disease might vary dependent on etiology and stage of disease.Further definitions of theγδT cell subsets in-volved in acute and chronic liver inflammation,as well as their effector cytokines might uncover whether interference withγδT cells could be a useful target for the treatment of liver disease.展开更多
The mechanisms involved in virus-induced severe hepatitis have not been fully elucidated. In this study, we investigated the role of gamma delta T cell receptors （γδ） T cells in the pathogenesis of fulminant viral...The mechanisms involved in virus-induced severe hepatitis have not been fully elucidated. In this study, we investigated the role of gamma delta T cell receptors （γδ） T cells in the pathogenesis of fulminant viral hepatitis （FVH） induced by murine hepatitis virus strain 3 （MHV-3）. The model of FVH was established by intraperitoneal injection of MHV-3 into Balb/cJ mice. The survival days of mice, and the serum levels of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were examined. The proportions of γδ T cells in blood, spleen and liver, and cytokines secreted by hepatic γδ T cells were analyzed by flow cytometry. The function of hepatic γδ T cells was examined by cytotoxicity assay. Balb/cJ mice died in 3 to 6 days post MHV-3 infection, with severe hepatic necrosis and significant augmentation of serum ALT and AST levels. The proportions of γδ T cells in blood, spleen and liver were significantly increased post MHV-3 infection, while those of the early activating molecule CD69-expressing γδ T cells and productions of cytokines tumor necrosis factor-alpha （TNF-α） and interferon-y （IFN-3,） increased remarkably in the liver. These highly activated liver γδ T cells were cytotoxic to MHV-3-infected hepatocytes in vitro and this effect of liver γδ T cells against hepatocytes might involve the TNF-α and IFN-γ pathway. These results demonstrated that γδ T cells might contribute to the pathogenesis of MHV-3-induced FVH through the effector cytokines TNF-α and IFN-γ. Key words： fulminant viral hepatitis; murine hepatitis virus strain 3; gamma delta T cell receptors T cells; tumor necrosis factor-a; interferon-α展开更多
The chemokine ligand 13-chemokine receptor 5(CXCL13-CXCR5)axis has been characterized as a critical tumor-promoting signaling pathway in the tumor microenvironment(TME)in multiple types of solid tumors.In this study,w...The chemokine ligand 13-chemokine receptor 5(CXCL13-CXCR5)axis has been characterized as a critical tumor-promoting signaling pathway in the tumor microenvironment(TME)in multiple types of solid tumors.In this study,we analyzed the expression profile of CXCL13 in kidney clear cell carcinoma(KIRC)and its correlation with tumor-infiltrating immune cells(TIICs).A monoclonal antibody against CXCL13 with high affinity and purity was generated in our lab for western blot and immunohistochemistry(IHC).Bioinformatic analysis was performed based on bulk-seq data from the Cancer Genome Atlas(TCGA)-KIRC and single-cell RNA-seq data from scRNASeqDB and PanglaoDB.Results showed that high CXCL13 expression in TME was associated with shorter progression-free survival(PFS),disease-specific survival(DSS),and overall survival(OS).KIRC cell lines,as well as several other cancer cell lines,had negative CXCL13 expression.IHC staining from the Human Protein Atlas(HPA)and our tissue array indicated that CXCL13 might be mainly expressed by TIICs,but not KIRC tumor cells.CXCL13 expression was strongly and positively correlated withγδT cell abundance in TME.Besides,γδT cell infiltration was associated with poor survival of KIRC.Methylation 450k array data showed that CXCL13 promoter hypomethylation was common in TIICs.The methylation level of cg16361705 within the CXCL13 promoter might play an important role in modulating CXCL13 transcription.In conclusion,our study revealed that CXCL13 expression andγδT cell infiltration in TME is associated with unfavorable survival of KIRC.TIICs,most possiblyγδT cells,are the dominant source of CXCL13 in KIRC TME.展开更多
Gamma/delta T cells (γδТ cells) are among the first lymphoid cells appearing in the ontogenesis. Many of γδТ cells are located in the small intestine/lamina propria of mice and human, where they cooperate with d...Gamma/delta T cells (γδТ cells) are among the first lymphoid cells appearing in the ontogenesis. Many of γδТ cells are located in the small intestine/lamina propria of mice and human, where they cooperate with different cells (B-1 cells, in particular) and influence their activity. However, such interactions are studied rather scanty, and the functional role of γδТ cells in the intestine?is not yet fully elucidated. To study the interactions of mouse γδТ cells with other cells it is necessary to have purified cell populations. Unfortunately, most approaches used for isolation of human γδТ cells are not suitable for isolation of mouse γδТ cells. The aim of the present study is the modification of the method of mouse intestinal γδТ cell isolation in the quantities sufficient for the in vivo and in vitro experiments.展开更多
文摘Primary cutaneous gamma-delta T-cell lymphoma (PCGD-TCL) is a very uncommon and extremely aggressive tumor, and is described in the newly re-vised World health organization for research and treatment of cancer classification of cutaneous lymphomas. A 43-year-old male patient presented with a 4 months history of cutaneous lesion over upper lip, without plaque and any constitutional symptom. Histopathological examination of skin biopsy revealed infiltration of atypical lymphocytes with hyperchromatic irregular nuclei. Immunophenotyping pattern of skin biopsy was compatible with PCGD-TLC. It is a highly aggressive tumor resistant to chemotherapy, immunotherapy, and radiation therapy. The GDTCL is characterized by a worse prognosis with a median survival of 15 months. Early diagnosis is essential and aggressive therapy is necessary.
基金Supported by The German Research FoundationNo.DFG Ta434/2-1 and SFB/TRR57the Interdisciplinary Center for Clinical Research(IZKF) Aachen
文摘Conventional adaptive T cell responses contribute to liver inflammation and fibrogenesis,especially in chronic viral infections and autoimmune hepatitis.However,the role of unconventional gamma-delta(γδ)T cells in liver diseases is less clear.In the past two decades,accumulating evidence revealed thatγδT cell numbers remarkably increase in the liver upon various inflammatory conditions in mice and humans.More recent studies demonstrated that the functional effect ofγδT cells on liver disease progression depends on the subsets involved,which can be identified by the expression of distinct T cell receptor chains and of specific cytokines.Fascinatingly,γδT cells may have protective as well as pathogenic functions in liver diseases.Interferonγ-producingγδT cells,for example,induce apoptosis in hepatocytes but also in hepatic tumor cells;while interleukin-17-expressingγδT cells can downregulate pathogenic effector functions of other immune cells and can promote apoptosis of fibrogenic stellate cells.However,the results obtained in human liver disease as well as murine models are not fully conclusive at present,and the effects ofγδT cells on the outcome of liver disease might vary dependent on etiology and stage of disease.Further definitions of theγδT cell subsets in-volved in acute and chronic liver inflammation,as well as their effector cytokines might uncover whether interference withγδT cells could be a useful target for the treatment of liver disease.
基金This project was supported by grants from the Chinese National Thirteenth Five Years Project in Science and Technology （No. 2017ZX10202201）, and Hubei Provincial Natural Science Foundation of China （No. 2018CFB206）.
文摘The mechanisms involved in virus-induced severe hepatitis have not been fully elucidated. In this study, we investigated the role of gamma delta T cell receptors （γδ） T cells in the pathogenesis of fulminant viral hepatitis （FVH） induced by murine hepatitis virus strain 3 （MHV-3）. The model of FVH was established by intraperitoneal injection of MHV-3 into Balb/cJ mice. The survival days of mice, and the serum levels of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were examined. The proportions of γδ T cells in blood, spleen and liver, and cytokines secreted by hepatic γδ T cells were analyzed by flow cytometry. The function of hepatic γδ T cells was examined by cytotoxicity assay. Balb/cJ mice died in 3 to 6 days post MHV-3 infection, with severe hepatic necrosis and significant augmentation of serum ALT and AST levels. The proportions of γδ T cells in blood, spleen and liver were significantly increased post MHV-3 infection, while those of the early activating molecule CD69-expressing γδ T cells and productions of cytokines tumor necrosis factor-alpha （TNF-α） and interferon-y （IFN-3,） increased remarkably in the liver. These highly activated liver γδ T cells were cytotoxic to MHV-3-infected hepatocytes in vitro and this effect of liver γδ T cells against hepatocytes might involve the TNF-α and IFN-γ pathway. These results demonstrated that γδ T cells might contribute to the pathogenesis of MHV-3-induced FVH through the effector cytokines TNF-α and IFN-γ. Key words： fulminant viral hepatitis; murine hepatitis virus strain 3; gamma delta T cell receptors T cells; tumor necrosis factor-a; interferon-α
基金funded by the National Science and Technology Major Project for Major New Drug Innovation and Development(2017ZX09302010).
文摘The chemokine ligand 13-chemokine receptor 5(CXCL13-CXCR5)axis has been characterized as a critical tumor-promoting signaling pathway in the tumor microenvironment(TME)in multiple types of solid tumors.In this study,we analyzed the expression profile of CXCL13 in kidney clear cell carcinoma(KIRC)and its correlation with tumor-infiltrating immune cells(TIICs).A monoclonal antibody against CXCL13 with high affinity and purity was generated in our lab for western blot and immunohistochemistry(IHC).Bioinformatic analysis was performed based on bulk-seq data from the Cancer Genome Atlas(TCGA)-KIRC and single-cell RNA-seq data from scRNASeqDB and PanglaoDB.Results showed that high CXCL13 expression in TME was associated with shorter progression-free survival(PFS),disease-specific survival(DSS),and overall survival(OS).KIRC cell lines,as well as several other cancer cell lines,had negative CXCL13 expression.IHC staining from the Human Protein Atlas(HPA)and our tissue array indicated that CXCL13 might be mainly expressed by TIICs,but not KIRC tumor cells.CXCL13 expression was strongly and positively correlated withγδT cell abundance in TME.Besides,γδT cell infiltration was associated with poor survival of KIRC.Methylation 450k array data showed that CXCL13 promoter hypomethylation was common in TIICs.The methylation level of cg16361705 within the CXCL13 promoter might play an important role in modulating CXCL13 transcription.In conclusion,our study revealed that CXCL13 expression andγδT cell infiltration in TME is associated with unfavorable survival of KIRC.TIICs,most possiblyγδT cells,are the dominant source of CXCL13 in KIRC TME.
文摘Gamma/delta T cells (γδТ cells) are among the first lymphoid cells appearing in the ontogenesis. Many of γδТ cells are located in the small intestine/lamina propria of mice and human, where they cooperate with different cells (B-1 cells, in particular) and influence their activity. However, such interactions are studied rather scanty, and the functional role of γδТ cells in the intestine?is not yet fully elucidated. To study the interactions of mouse γδТ cells with other cells it is necessary to have purified cell populations. Unfortunately, most approaches used for isolation of human γδТ cells are not suitable for isolation of mouse γδТ cells. The aim of the present study is the modification of the method of mouse intestinal γδТ cell isolation in the quantities sufficient for the in vivo and in vitro experiments.
