EFFECTS OF INTERLEUKIN-12 ON THE INDUCTION OF CYTOTOXIC T-LYMPHOCYTESFROM THE REGIONAL LYMPH-NODE LYMPHOCYTES OF PATIENTS WITH LUNG ADENOCARCINOMA

Lung cancer-specific cytotoxic T lymphocytes (CTL) were induced by rep eated stimulations of regional lymph node lymphocytes (RLNL) in lung c ancer patients with either autologous or HLA-A-locus-matched tumor cel ls, To investigate the effect of interleukin-12 (IL-12), IL-12 was add ed during the stimulation of RLNL from HLA A24 / adenocarcinoma patien ts with either autologous tumor cells or HLA A24-positive adenocarcino ma cells (PC-9) in combination with, or instead of interleukin-2 (IL-2 ), and then the cytotoxic activity, cytokine production and population s of the lymphocyte subsets were examined, The addition of IL-12, or t he substitution of IL-2 by IL-12 was found to enhance the cytotoxic ac tivity and the cytokine production (IFN-gamma, GM-CSF) of the CTL as c ompared with IL-2 alone, The cytotoxic activity and cytokine productio n were both partially inhibited by anti-MHC-class I monoclonal antibod y, The CTL thus induced by IL-12 had a higher proportion of CD3(+)/CD5 6(+) cells than the CTL induced with IL-2 alone, The positively select ed CD8(+)/CD56(-) lymphocytes showed PC-9-specific cytotoxic activity, because the population did not show any cytotoxicity to K562 or A549 (HLA-A26/A30). However, the CD3(+)/CD56(+) lymphocytes were cytotoxic to both PC-9 and K562, In conclusion, IL-12 is considered to be a usef ul cytokine for both the induction of lung-cancer specific CTL and the augmentation of non-MHC-restricted cytotoxicity against tumor cells, and may be applicable for adoptive immunotherapy using CTL.