Suppression of immune surveillance in melanoma.
Numerous reports of IL-10 cytokine secretion by tumor infiltrating cells indicate there is suppression of immune surveillance within the milieu of many melanomas. In this paper we have outlined the suppressor system that best fits the published data. The regulatory system is composed of CD4+ T-lymphocytes which have been activated and programmed to secrete Th2 cytokines. Initially these cells do not secrete cytokines, but subsequently they enter an IL-10 secretory phase as a result of T-T cell interaction. After activation, Th1 programmed T-cells express MHC class II molecules and B7 second signals. When these Th1 T-cells express MHC II molecules containing 'self' polypeptides coupled with faulty B7-H1 second signals they are subject to inactivation by Th2 T-cells. If this system can be inactivated, immunotherapy of melanoma will be more successful. If an antigen can be discovered that stimulates sensitized Th2 T-cells without stimulating Th1 T-cells, this antigen, followed with cyclophosphamide, can be used to destroy the Th2 T-cells in the course of both active and passive immunotherapy. Solubilized MHC II molecules with appropriate 'self' polypeptides should qualify as such an antigen. We postulate such an antigen can be prepared using poliovirus 1 (Sabin) to lyse melanoma tissue cultures.
Biggs
M W
MW
Health Services Department, Lawrence Livermore National Laboratory, Livermore, California, 94550, USA.
Eiselein
J E
JE
D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D007167:Immunotherapy; D016753:Interleukin-10 / Q000378:metabolism; D008545:Melanoma / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D018417:Th1 Cells / Q000276:immunology
D000949:Histocompatibility Antigens Class II; D016753:Interleukin-10