Regulatory T cell depletion enhances tumor specific CD8 T-cell responses, elicited by tumor antigen NY-ESO-1b in hepatocellular carcinoma patients, in vitro.
Immunotherapy in hepatocellular carcinoma based on one or a few tumor specific antigens have shown limited antitumor efficacy. As a major suppressive factor in tumor immune response, better understanding of the role of regulatory T cells (Tregs) in hepatocellular carcinoma might be important for design of future immunotherapy-based clinical protocols. Tregs from 49 HCC patients and 40 controls were identified by flow cytometric analysis for the phenotype. Functional studies were performed by analyzing their inhibition to immune responses. Finally investigating whether elimination of Tregs was capable of enhancing the immunostimulatory efficacy of NY-ESO-1b peptides. In HCC peripheral blood and tumor-infiltrating lymphocytes, we found increased numbers of Tregs, which expressed high levels of HLA-DR, GITR and CD103. The prevalence of Tregs increased with during progressive stages in HCC patients. Moreover, the elimination of Treg cells followed by stimulating with NY-ESO-1b peptide significantly improved the anti-tumor cytotoxic T lymphocytes responses in HCC patients compared with stimulating with NY-ESO-1b peptide alone. The immune response efficiency increased from 37.5 to 62.5%. In conclusion, the increase in frequency of Treg cells might play a role in suppression of the immune response against HCC and for the design of immunotherapy the incorporation of the Treg cell depletion strategy will achieve potent anti-tumor immunity with therapeutic impact.
Zhang
Heng-Hui
HH
Hepatology Institute, Peking University, People's Hospital, Beijing 100044, P.R. China.
Mei
Ming-Hui
MH
Fei
Ran
R
Liao
Wei-Jia
WJ
Wang
Xue-Yan
XY
Qin
Li-Ling
LL
Wang
Jiang-Hua
JH
Wei
Lai
L
Chen
Hong-Song
HS
D000328:Adult; D015703:Antigens, CD / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000628:therapy*; D016022:Case-Control Studies; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D053450:Glucocorticoid-Induced TNFR-Related Protein; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping / Q000379:methods; D039001:Integrin alpha Chains / Q000276:immunology; D008113:Liver Neoplasms / Q000276:immunology / Q000628:therapy*; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion / Q000379:methods*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000276:immunology* / Q000627:therapeutic use; D010446:Peptide Fragments / Q000276:immunology* / Q000627:therapeutic use; D017475:Receptors, Nerve Growth Factor / Q000276:immunology; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D013997:Time Factors; D019139:Tumor Escape; D055815:Young Adult
D015703:Antigens, CD; D019496:Cancer Vaccines; D053450:Glucocorticoid-Induced TNFR-Related Protein; D006684:HLA-DR Antigens; D039001:Integrin alpha Chains; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C491405:TNFRSF18 protein, human; C091367:alpha E integrins; C504237:peptide NY-ESO-1 157-165