Symposium: Cellular Immunity and the Immunotherapy of Cancer: Tolerance and Activation: PDF OnlyBaskar Sivasubramanian; Nabavi, Nasrin; Glimcher, Laurie H.; Ostrand-Rosenberg, SuzanneJournal of Immunotherapy with Emphasis on Tumor Immunology: October 1993 - p 209-215 Buy Abstract Summary In previous studies we have shown that the highly malignant mouse Sal sarcoma can be converted into an immunogenic tumor that is immunologically rejected by the autologous host if the tumor cells are transfected with and express syngeneic major histocompatibility complex (MHC) class II genes. Tumor cells expressing class II heterodimers truncated for the cytoplasmic regions of the α and β chains, however, are as malignant as wild-type class II ~ tumors. These studies have contributed to the hypothesis that T-cell activation requires two signals: the engagement of the MHC class II/peptide complex of the antigen-presenting cell (APC) by the T cell receptor for antigen of the responding T cell and the transmittal of a second, or costimulatory, signal by the APC to the responding T cell. In this report we show that induction of tumor-specific immunity is facilitated by delivery of a costimulatory signal provided by the B7 activation molecule. Mice challenged with Sal cells bearing truncated class II molecules and transfected with B7 cDNA are immune to the transfectants and are protected against a challenge of wild-type class II-B7- ascites or solid Sal tumor. The induced immunity requires CD4+ T cells and is specific for the immunizing sarcoma cells. These results highlight the critical role of the B7 costimulatory pathway in stimulating long-term, tumor-specific immunity that is effective against high doses of challenging wild-type tumor and suggest a strategy for enhancing tumor rejection. © Lippincott-Raven Publishers.