HUMAN MELANOMA-SPECIFIC, NONCYTOLYTIC CD8-CELLS THAT CAN SYNTHESIZE TYPE-I CYTOKINE( T)

The existence of CD8+ CTLs that are capable of recognizing MHC class I -bound, human tumor-associated peptide antigens is now unequivocally d ocumented in cancer patients, Thus far, the role of CD8+ T cells in tu mor immunity has been predominantly viewed in terms of cytolytic abili ty as the prime mode of their function. Interestingly, it is increasin gly evident that CD8+ T cells are capable of synthesizing both type I and type II cytokines, Thus, it is conceivable that tumor antigen-spec ific but noncytolytic CD8+ T cells might play an important role in ant itumor immune response by synthesizing type I cytokine, Through such c ytokines, they could provide ''help'' for the process of generating as well as in maintaining an effective CD8+ CTL response, In addition, t hey might recruit other types of effector cells (such as natural kille r cells, macrophages, and others) locally at the tumor site. Either wa y, they could exert a profoundly positive role in cell-mediated antitu mor immune response, particularly because the great majority of tumor cells express only MHC class I molecules that present peptide epitopes to CD8+ T cells, Unfortunately, tumor antigen-specific, noncytolytic but type I cytokine-secreting CD8+ T cells have not received much inve stigative attention, Here we show that CD8+ T cells, isolated from the tumor-infiltrating lymphocytes from human melanoma, synthesize type I cytokine (IFN-gamma and tumor necrosis factor alpha) in a MHC class I -restricted and tumor-specific noncytolytic interaction with the autol ogous melanoma cells.