title: The paradoxical changes of membrane and soluble herpes virus entry mediator in hepatocellular carcinoma patients.
abstract: OBJECTIVE
  The herpes virus entry mediator (HVEM) network has become new directions in targeting novel checkpoint inhibitors for cancer therapy. However, the changes of membrane-bound HVEM (mHVEM) and soluble HVEM (sHVEM) in hepatocellular carcinoma (HCC) are not fully understood. This study aims to study the changes of mHVEM and sHVEM in HCC patients.
  
  
  METHODS
  Serum samples were collected from 65 HCC patients, from which sHVEM levels were examined by enzyme-linked immunosorbent assay. Expressions of mHVEM on peripheral lymphocytes from 20 HCC patients were determined using flow cytometry, and associations between mHVEM on T and B cells were analyzed.
  
  
  RESULTS
  The levels of mHVEM were downregulated on peripheral lymphocytes in HCC patients, with a strong positive correlation between mHVEM expression on T and B cells. In contrast, the levels of soluble HVEM were upregulated in the serum of HCC patients. Furthermore, we found that the increase in sHVEM level was correlated with advanced stages HCC.
  
  
  CONCLUSIONS
  Our data demonstrated paradoxical changes of membrane and soluble HVEM in the peripheral blood of HCC patients for the first time. These data supported the notion that roles of HVEM are likely to be immunosuppressive rather than activating tumor immunity. Future studies are warranted to further explore the translational values of mHVEM and sHVEM in peripheral blood as diagnostic markers and therapeutic targets.
authors.affiliation: Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.|Guangdong Key Laboratory of Liver Disease Research, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Qiyi
authors.identifier: http://orcid.org/0000-0003-0649-0437
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Geng-Lin
authors.initials: GL
authors.lastname: Zhang
authors.affiliation: Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Di
authors.initials: D
authors.lastname: Su
authors.affiliation: Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Zhan-Lian
authors.initials: ZL
authors.lastname: Huang
authors.affiliation: Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Zhao-Xia
authors.initials: ZX
authors.lastname: Hu
authors.affiliation: Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.|Cell-gene Therapy Translational Medicine Research Center, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Peng
mesh_terms: D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000175:diagnosis / Q000276:immunology / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D008113:Liver Neoplasms / Q000097:blood / Q000175:diagnosis / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D053240:Receptors, Tumor Necrosis Factor, Member 14 / Q000097:blood* / Q000378:metabolism* / Q000502:physiology; D013601:T-Lymphocytes / Q000378:metabolism; D055815:Young Adult
chemical_list: D015415:Biomarkers; D053240:Receptors, Tumor Necrosis Factor, Member 14
keywords: HVEM; hepatocellular carcinoma; lymphocytes; soluble HVEM