THE ROLE OF MAJOR HISTOCOMPATIBILITY COMPLEX EXPRESSION ON HEAD AND NECK-CANCER CELLS IN THE INDUCTION OF AUTOLOGOUS CYTOTOXIC T-LYMPHOCYTES

Using head and neck tumors, we studied the role of HLA class I and DR antigens on tumor cells in cytotoxic T lymphocyte (CTL) induction. Exp ression of major histocompatibility complex (MHC) antigens was investi gated by two-color flow cytometry analysis and for this study we used the tumor cells, over 50% of which expressed both HLA class I and DR a ntigens on their surface. In seven cases, tumor cells were divided int o three groups according to the specificity of monoclonal antibodies ( mAb) to MHC to study the role of MHC antigens on tumor cells in CTL in duction: one was not blocked (MHC double-positive tumor), a second was blocked by anti-class I mAb (class-I-negative DR-positive tumor) and third was blocked by anti-DR mAb (class-I-positive DR-negative tumor). Subsequently, these tumors were used to stimulate an autologous mixed lymphocyte/tumor cell culture for 5 days (MLTC) followed by further c ultivation with interleukin-2 for 12 days. The induced autologous tumo r killer cells were most cytotoxic when non-treated tumors, which cons ist mainly of cells that are both HLA-class I and DR-positive, were us ed as stimulator cells. When the tumor cells blocked by anti-DR mAb we re used as stimulators, autologous tumor killer activity was lower tha n that induced by tumor cells blocked by anti-class-I mAb. Moreover, c ytolysis by autologous tumor killer cells induced by stimulation of no n-treated tumor cells was blocked during the effector phase, 26.6%-42. 3% and 32.7%-53.8% by anti-class-I and anti-DR mAb respectively, sugge sting that majority of the autologous tumor killer cells are MHC-restr icted CD8+ or CD4+ CTL. These results suggest that both MHC class I an d class II antigens on head and neck tumor cells play a critical role in inducing CTL.