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glutamine deprivation impairs function of infiltrating CD8^(+)T cells in hepatocellular carcinoma by inducing mitochondrial damage and apoptosis

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World Journal of gastrointestinal Oncology 2022年第6期14卷 1124-1140页

作者： Wei Wang Meng-Nan guo Ning Li De-Quan Pang Jing-Hua Wu Department of Laboratory Medicine Tangshan Maternal and Child Health Care HospitalNorth China University of Science and TechnologyTangshan 063000Hebei ProvinceChina Department of Laboratory Medicine North China University of Science and Technology Affiliated HospitalTangshan 063000Hebei ProvinceChina Department of Oncology North China University of Science and Technology Affiliated HospitalTangshan 063000Hebei ProvinceChina

BACKgROUND The functions of infiltrating CD8^(+)T cells are often impaired due to tumor cells causing nutrient deprivation in the tumor ***,the mechanisms of CD8^(+)T cell dysfunction have become a hot research topic,and there is increased interest on how changes in metabolomics correlate with CD8^(+)T cell *** To investigate whether and how glutamine metabolism affects the function of infiltrating CD8^(+)T cells in hepatocellular *** Immunohistochemical staining and immunofluorescence were performed on surgically resected liver tissues from *** expressed genes in infiltrating CD8^(+)T cells in hepatocellular carcinoma were detected using RNA *** CD8^(+)T cells were co-cultured with Huh-7 cells for 3 *** function and mitochondrial status of CD8^(+)T cells were analyzed by flow cytometry,quantitative real-time polymerase chain reaction,and transmission electron ***,CD8^(+)T cells were treated with the mitochondrial protective and damaging *** alterations in CD8^(+)T cells were detected by flow ***,complete medium without glutamine was used to culture cells and their functional changes and mitochondrial status were *** There were a large number of infiltrating PD-1+CD8^(+)T cells in liver cancer ***,we cocultured CD8^(+)T cells and Huh-7 cells to explore the regulatory effect of hepatoma cells on CD8^(+)T *** cytometry results revealed increased PD-1 expression and decreased secretion of perforin(PRF1)and granzyme B(gZMB)by CD8^(+)T cells in the co-culture ***,JC-1 staining was decreased and the levels of reactive oxygen species and apoptosis were increased in CD8^(+)T cells of the co-culture group;additionally,the mitochondria of these cells were *** CD8^(+)T cells were treated with the mitochondrial protective and damaging agents,their function was restored and inhibited,respectively,through the mit

关键词： glutamine Mitochondrial damage CD8^(+)T cells T cell function Hepatocellular carcinoma

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Evaluation of high-risk factors and the diagnostic value of alpha-fetoprotein in the stratification of primary liver cancer

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World Journal of Clinical Cases 2022年第26期10卷 9264-9275页

作者： Hong-Bin Jiao Wei Wang Meng-Nan guo Ya-Li Su De-Quan Pang Bao-Lin Wang Jun Shi Jing-Hua Wu Clinical Laboratory Tangshan Maternal and Child Health Care HospitalNorth China University of Science and TechnologyTangshan 063000Hebei ProvinceChina Department of Oncology Tangshan Maternal and Child Health Care HospitalNorth China University of Science and TechnologyTangshan 063000Hebei ProvinceChina Clinical Laboratory Tangshan Nanhu HospitalTangshan 063000Hebei ProvinceChina

BACKgROUND Alpha-fetoprotein(AFP)is one of the diagnostic standards for primary liver cancer(PLC);however,AFP exhibits insufficient sensitivity and specificity for diagnosing *** To evaluate the effects of high-risk factors and the diagnostic value of AFP in stratified *** In total,289 PLC cases from 2013 to 2019 were selected for ***,the contributions of high-risk factors in stratifying PLC were compared according to the following criteria:Child–Pugh score,clinical stage of liver cirrhosis,tumor size,and Barcelona Clinic Liver Cancer(BCLC)***,the diagnostic value of AFP was evaluated in different stratifications of PLC by receiver operating characteristic *** PLC cases in which AFP played little role,the diagnostic values of carcinoembryonic antigen(CEA),carbohydrate antigen 19-9(CA 19-9),gamma-glutamyl transferase(ggT),and AFP were *** The roles of high-risk factors differed in stratified *** incidence of smoking and drinking history was higher in PLC with Child–Pugh scores of C(Pge tumors(Pge D PLC was more likely to be associated with HBV infection and cirrhosis(Pgher in PLC with cirrhosis,diffuse tumors,and BCLC stage D *** diagnosing PLC defined as Child–Pugh A,B,and C,massive hepatoma,diffuse hepatoma,BCLC stage B,C,and D,and AFP showed significant diagnostic value[all area under the curve(AUC)>0.700].However,these measures were meaningless(AUCge PLC,but could be replaced by the combined detection of CEA,CA 19-9,ggT,and AFP(AUC=0.810 and 0.846,respectively).CONCLUSION Stratification of PLC was essential for precise diagnoses and benefited from evaluating AFP levels.

关键词： Primary liver cancer Stratification Risk factors Alpha-fetoprotein Receiver operating characteristic curve Diagnostics

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