IL-12 directly up-regulates the expression of HLA class I, HLA class II and ICAM-1 on human melanoma cells: a mechanism for its antitumor activity?
IL-12 enhances cytolytic activity and proliferation of NK and T cells, and induces cytokines such as IFN-gamma. No direct effects on non-hematopoietic cells have been shown. This study investigates the effects of IL-12 on melanoma cells in vitro. We analyzed 15 melanoma cell cultures and 1 melanoma cell line. Out of 16 samples 13 expressed the beta chain of the IL-12 receptor (IL-12Rbeta). Preincubation with IL-12 increased the surface levels of human leukocyte antigen (HLA) class I, HLA class II and intercellular adhesion molecule (ICAM)-1 of those cultures with IL-12Rbeta expression. The effects of IL-12 on HLA class I could be blocked by an IL-12-neutralizing monoclonal antibody (mAb), but not by an mAb against IFN-gamma. Melanoma cells transduced with IL-12 expressed enhanced levels of HLA class I, HLA class II and ICAM-1 compared to controls. Co-incubation of the melanoma cells with allogeneic peripheral blood mononuclear cells (PBMC) resulted in enhanced proliferation and increased production of IL-2 and IFN-gamma after pretreatment with IL-12. IL-12 pretreatment increased the susceptibility of melanoma cells to lysis by prestimulated autologous PBMC. Since IL-12 induced immunocritical surface molecules on melanoma cells, it might be beneficial during immune interventions in melanoma patients.
Yue
F Y
FY
Department of Dermatology, University of Zürich Medical School, Switzerland.
Geertsen
R
R
Hemmi
S
S
Burg
G
G
Pavlovic
J
J
Laine
E
E
Dummer
R
R
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D001324:Autoantigens; D018122:B7-1 Antigen / Q000235:genetics; D005822:Genetic Vectors; D006680:HLA Antigens / Q000378:metabolism*; D006681:HLA-D Antigens / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D007371:Interferon-gamma / Q000037:antagonists & inhibitors; D018664:Interleukin-12 / Q000235:genetics / Q000494:pharmacology*; D007519:Isoantigens; D008213:Lymphocyte Activation; D008545:Melanoma / Q000276:immunology* / Q000628:therapy; D009500:Neutralization Tests; D018123:Receptors, Interleukin / Q000378:metabolism; D053707:Receptors, Interleukin-12; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D001324:Autoantigens; D018122:B7-1 Antigen; D006680:HLA Antigens; D006681:HLA-D Antigens; D015395:Histocompatibility Antigens Class I; D007519:Isoantigens; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D018799:Intercellular Adhesion Molecule-1; D018664:Interleukin-12; D007371:Interferon-gamma