Hyperthermia improves cellular immune response to human hepatocellular carcinoma subsequent to co-culture with tumor lysate pulsed dendritic cells.
Dendritic cells play a major role in cellular immunity. The crucial steps of antigen presentation and processing by DCs may be limiting factors for adoptive cellular immunotherapy. Here, we investigated whether hyperthermia of human hepatocellular carcinoma (HCC) cells induces enhanced cytotoxic cellular immune response. Peripheral blood mononuclear cell (PBMC)-derived DCs were pulsed with tumor cell lysate of the human HCC cell line HepG2, which had been heat shocked prior to incubation for 5 h. Subsequent to TNFalpha-induced maturation DCs were co-cultured with autologous CD4+ and/or CD8+ cells, and T cell mediated cytolysis of HepG2 cells was assessed. We observed enhanced CD4+/8+ cellular cytotoxicity against HepG2 cells subsequent to co-culture with the heat shocked tumor lysate pulsed DCs as compared to pulsing DCs with lysate of non-heat shocked tumor cells. The improved cellular immune response can be related to enhanced expression of HSP 70 and 90 in HepG2 cells upon hyperthermia.
Department of Radiology, University Hospital of Vienna Medical School, A-1090 Vienna, Austria. gerd.schueller@univie.ac.at
Gerd
G
Schueller
Anton
A
Stift
Josef
J
Friedl
Peter
P
Dubsky
Thomas
T
Bachleitner-Hofmann
Thomas
T
Benkoe
Raimund
R
Jakesz
Michael
M
Gnant
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D006528:Carcinoma, Hepatocellular / Q000276:immunology* / Q000628:therapy*; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D006358:Hot Temperature; D006801:Humans; D006979:Hyperthermia, Induced; D016219:Immunotherapy, Adoptive; D008113:Liver Neoplasms / Q000276:immunology* / Q000628:therapy*; D008214:Lymphocytes / Q000276:immunology; D018448:Models, Immunological; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D014409:Tumor Necrosis Factor-alpha