1. Cytokine and kinase regulation of the generation of anti-tumor killer cells: IL-2 and IL-4 mediate through two distinct kinase pathways to induce the generation of CD3-induced activated killer cells, CD3-AK. IL-2 promoted CD3-AK cell response is mediated through a PKC- (protein kinase C) dependent pathway, and IL-4 promoted CD3-AK cell response is mediated through a PTK- (protein tyrosine kinase) dependent pathway. These two pathways can compliment each other to generate CD3-AK cells. 2. Effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) gene transfer on the tumorigenicitiy and immunogenicity of B16 melanoma: Transduction of murine B16 melanoma cells with a GM-CSF gene, the B16-MG tumor line, showed reduced tumorigenicity. In vitro studies demonstrated no remarkable difference between the parent and transduced tumor lines in immunogenicity or immunosensitivity. In the in vivo tumor transplantation study, the B16-MG cell line was not only more immunogenic but also was more immunosensitive than the parent line. The in vivo protective effect was specific for B16 tumor. Both CD4+ and CD8+ cells were required for in vivo protection. The tumor bearing hosts could generate anti-tumor killer cells, hence the development of progressive growth of B16 tumor was not due to the lack of anti-tumor immune response. It appears that the overall effect of in vivo tumor immunity is determined by a complex network of interactions among different compartments of host immune cells and different immuno-regulatory molecules derived from the host and from the tumor. 3. Tumor cell-induced immunosuppression: To study the nature of the tumor-cell induced immunosuppression, we examined the lymphocytes obtained from the malignant pleural effusion (EAL) of lung cancer patients. The EAL were in a generally immunosuppressed state that they failed to kill three different tumor targets. However, treatment of EAL with both IL-2 and CD3 fully restored the cytolytic activity of the EAL to kill the autologous tumor target but not other tumor targets, suggesting that the restored cytolytic reaction was tumor specific and CTL anergy might be induced at localized site in vivo.
