Interleukin-12 augments cytolytic activity of peripheral blood mononuclear cells against autologous lung cancer cells in combination with IL-2.
The majority of patients with advanced lung cancer die within a few years. Accordingly, new therapeutic modalities need to be developed. Interleukin (IL)-12 was previously known as natural killer (NK) cell stimulatory factor or cytotoxic lymphocyte maturation factor. By virtue of its effects on T cells and NK cells, IL-12 seems to be one of the key cytokines that regulates cell-mediated anti tumor immune responses. Recently, there has been a substantial interest in the potential applications of IL-12 in the treatment of lung cancer. However, there have been no reports about the effect of IL-12 on peripheral blood mononuclear cells (PBMCs) obtained from lung cancer patients in an autologous setting. In this study, we examined the cytotoxicity of PBMC activated by IL-2, IL-12 or both against K562 or autologous lung cancer cells. In contrast to the effect of IL-2 on NK activity, IL-12 alone augmented NK activity against K562 cells, but not against autologous lung cancer cells. IL-12 augmented the IL-2 mediated cytotoxicity of PBMC against both K562 and autologous lung cancer cells. In the absence of IL-2, IL-12 alone cannot induce an autologous anti-tumor effect in vivo. In summary, our results clearly demonstrated that IL-12 can augment the cytolytic activity of PBMC against K562 and autologous lung cancer cells when combined with IL-2, although, IL-12 alone was unable to induce a marked increase in the cytotoxicity against autologous lung cancer cells. These results suggest that an administration of IL-12 in combination with IL-2 may be a useful therapeutic option for solid tumors.
Hiraki
Akio
A
Department of Medicine (II), Okayama University Medical School, 2-5-1 Shikata-cho, Okayama 700-8558, Japan. ahiraki@md.okayama-u.ac.jp
Kiura
Katsuyuki
K
Yamane
Hiromichi
H
Nogami
Naoyuki
N
Tabata
Masahiro
M
Takigawa
Nagio
N
Ueoka
Hiroshi
H
Tanimoto
Mitsune
M
Harada
Mine
M
D000368:Aged; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D018664:Interleukin-12 / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology* / Q000627:therapeutic use; D007376:Interleukin-2 / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology* / Q000627:therapeutic use; D020014:K562 Cells; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology; D008175:Lung Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D008213:Lymphocyte Activation / Q000187:drug effects; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D014407:Tumor Cells, Cultured
D007376:Interleukin-2; D018664:Interleukin-12