INTERFERON-GAMMA INHIBITS TUMOR-ANTIGEN PRESENTATION BY EPIDERMAL ANTIGEN-PRESENTING CELLS

Murine I-A(+) epidermal antigen-presenting cells (APCs) have been show n to be capable of presenting soluble tumor fragments (TFs), as a sour ce of tumor-associated antigens (TAAs), for primary and secondary tumo r immune responses. In this study we investigated whether incubation o f epidermal APCs in interferon-gamma (IFN-gamma) modulates their abili ty to present TAA and whether the effects of IFN-gamma on the presenta tion of tumor antigen correspond to its effects on alloantigen present ation in both primed and unprimed systems. Our results show that three weekly subcutaneous injections of naive mice with GM-CSF-cultured but not with fresh TAA-pulsed epidermal APCs induce protective tumor immu nity in naive mice and that the immunostimulatory effect of GM-CSF in this system is abrogated by coculture of epidermal cells in IFN-gamma. Furthermore, epidermal APCs are able to present TAA to primed, tumor- immune mice, as assessed by the elicitation of tumor-specific delayed- type hypersensitivity after injection of TAA-pulsed epidermal APCs. IF N-gamma was found to inhibit tumor antigen presentation by freshly pre pared epidermal APCs in this system. The effects of IFN-gamma on the p resentation of tumor antigen correlated well with its effects on the p rimary and secondary mixed epidermal cell-lymphocyte reaction, indicat ing that IFN-gamma differentially modulates the function of epidermal APCs with regard to induction versus elicitation of immunity.