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-gamma, 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.
Hanagiri
T
T
Department of Surgery II, School of Medicine, University of Occupational and Environmental Health, Kitakyushu.
Yoshino
I
I
Takenoyama
M
M
So
T
T
Fujie
H
H
Imabayashi
S
S
Eifuku
R
R
Yoshimatsu
T
T
Osaki
T
T
Nakanishi
R
R
Ichiyoshi
Y
Y
Nagashima
A
A
Nomoto
K
K
Yasumoto
K
K
D000230:Adenocarcinoma / Q000188:drug therapy / Q000276:immunology* / Q000628:therapy*; D000368:Aged; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005434:Flow Cytometry; D015234:HLA-A Antigens / Q000276:immunology; D006801:Humans; D016219:Immunotherapy, Adoptive; D018664:Interleukin-12 / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000628:therapy*; D008198:Lymph Nodes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D014407:Tumor Cells, Cultured
D016207:Cytokines; D015234:HLA-A Antigens; D018664:Interleukin-12