title: Expansion of peripheral and intratumoral regulatory T-cells in hepatocellular carcinoma: a case-control study.
abstract: BACKGROUND
  Hepatocellular carcinoma (HCC) is notorious for poor prognosis with limited therapeutic options. A better understanding of the role of regulatory T-cells (Tregs) in HCC is important for design of immunotherapy based clinical protocol. The objective of the present study was to evaluate the presence of Tregs in tumor microenvironment in patients with HCC compared to chronic hepatitis (CH).
  
  
  METHODS
  The frequency of CD4 + CD25 + Treg cells was evaluated from peripheral blood (PB) of 28 patients of HCC and 30 controls including CH cases and healthy donors using flowcytometry. Intratumoral Treg were also analyzed in tissue samples from 17 HCC cases and 15 CH cases. In addition the expression of FOXP3 and CTLA-4 was also studied by RT-PCR.
  
  
  RESULTS
  Frequency of CD4 + CD25 + cells in the PBMCs of HCC cases was significantly higher than in HC (10.8 ± 7.64 vs 3.05 ± 1.30, P < 0.005) and CH patients (2.88 ± 1.92, P < 0.005). Also Treg population was significantly higher in HCC tumor microenvironment compared to CH biopsies (15.8 ± 5.32 vs 5.51 ± 3.40, P < 0.05). Expression of FOXP3 and CTLA-4 was also significantly higher in HCC patients ( P < 0.05) compared to CH group.
  
  
  CONCLUSIONS
  We provide evidence of an increased population of Treg not only in the PB but also in tumor microenvironment of HCC patients, suggesting association of enhanced Treg activity with poor immune responses to tumor antigens. These findings may in future play a significant role in designing immunotherapeutic approaches in HCC.
authors.affiliation: Department of Immunopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Sapna
authors.initials: S
authors.lastname: Thakur
authors.forename: Anuj
authors.initials: A
authors.lastname: Singla
authors.forename: Yogesh
authors.initials: Y
authors.lastname: Chawla
authors.forename: Arvind
authors.initials: A
authors.lastname: Rajwanshi
authors.forename: Naveen
authors.initials: N
authors.lastname: Kalra
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Arora
mesh_terms: D000328:Adult; D015704:CD4 Antigens / Q000032:analysis; D060908:CTLA-4 Antigen / Q000032:analysis; D006528:Carcinoma, Hepatocellular / Q000276:immunology* / Q000473:pathology*; D016022:Case-Control Studies; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000032:analysis; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D008099:Liver / Q000473:pathology*; D008113:Liver Neoplasms / Q000276:immunology* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000737:chemistry / Q000276:immunology*
chemical_list: D015704:CD4 Antigens; D060908:CTLA-4 Antigen; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit