Surrogate markers of antitumor responses: In vitro activation of T cells by autologous tumor peptides

The increasing ability to augment antitumor immunity in model:systems has l ed to increased numbers of clinical trials. However, progress in detecting immune responses by patients against autologous tumors has been slow, Altho ugh a considerable number of tumor antigens, as well as peptides derived fr om them, and the MHC determinants together with which they are presented ha ve been identified for melanoma, this is not so for the majority of solid t umors. Furthermore, tumor cells themselves are poor stimulators of immunity . Thus, approaches that do not depend upon defined antigens or using tumor cells as stimulators would be desirable. To attempt to measure immune respo nses in these situations, we tested whether total peptides, prepared from a utologous tumor tissue, stimulated cytokine release by T cells. Peripheral blood mononuclear cells (PBMCs) were mixed with antigen-presenting cells (A PCs), pulsed with tumor peptides, and tested in the ELISPOT assay for IFN-g amma secretion. Few spots were obtained when PBMCs were cultured with unpul sed APCs or in wells with peptide-pulsed APC alone. In contrast, a strong r esponse was seen when PBMCs were cultured with APCs that had been pulsed wi th autologous total tumor peptides, This system should help to identify tho se immunotherapeutic approaches that induce responses against tumor cells i n vivo. Because different cytokine profiles are associated with distinct ar ms of the immune response, testing in the ELISPOT assay may also help us un derstand the mechanisms responsible.