Effects of Interleukin‐12 on the Induction of Cytotoxic T Lymphocytes from the Regional Lymph Node Lymphocytes of Patients with Lung Adenocarcinoma

Lung cancer‐specific cytotoxic T lymphocytes (CTL) were induced by repeated stimulations of regional lymph node lymphocytes (RLNL) in lung cancer patients with either autologous or HLA‐A‐locus‐matched tumor cells. To investigate the effect of interleukin‐12 (IL‐12), IL‐12 was added during the stimulation of RLNL from HLA A24 / adenocarcinoma patients with either autologous tumor cells or HLA A24‐positive adenocarcinoma cells (PC‐9) in combination with, or instead of interleukin‐2 (IL‐2), and then the cytotoxic activity, cytokine production and populations of the lymphocyte subsets were examined. The addition of IL‐12, or the substitution of IL‐2 by IL‐12 was found to enhance the cytotoxic activity and the cytokine production (IFN‐γ, GM‐CSF) of the CTL as compared with IL‐2 alone. The cytotoxic activity and cytokine production were both partially inhibited by anti‐MHC‐class I monoclonal antibody. The CTL thus induced by IL‐12 had a higher proportion of CD3(+)/CD56(+) cells than the CTL induced with IL‐2 alone. The positively selected 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 useful 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.