TUMOR-CELL RECOGNITION BY LYMPHOCYTES - IS THE MHC ALWAYS ESSENTIAL

Phenotypic and functional analyses of tumor-infiltrating lymphocytes ( TILs) used in clinical trials revealed that cells other than CTLs can have antitumor efficacy. This observation led us to search for mechani sms for tumor recognition by lymphocytes that utilize alternatives to surface structures of tumor cells, for example, MHC antigen complexes; the latter are generally believed to be the immunogenic platforms for CTLs. Therefore, as a possible source of immunostimulatory activity, we compared the ability of plasma membrane components of tumor cell li nes with first secreted tumor cell components and then intracellular t umor components to act as mitogenic sources for human TIL lints. Surpr isingly, the latter was found to be most potent, particularly Oncoimmu nin-L, which is a 45-kDa protein with sequence similarity to members o f the serpin family of proteins. This protein, which has at least a 31 % sequence identity to human leukocyte elastase inhibitor and stimula tes [H-3]-thymidine incorporation into the DNA of human TILs, may be f ound in the cytosol of many tumor cells. Taken together with our earli er work in which a 36-kDa protein, also of tumor cytosolic origin, was shown to induce differentiation of myeloid cells, we propose soluble factors derived from tumor cells as a pathophysiological source of tum or immunogenicity. Moreover, detailed biochemical and biophyscial char acterization of tumor cell immunocyte interactions will define the tum or immunoenvironment.