Journal of Clinical Oncology, 2004 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 22, No 14S (July 15 Supplement), 2004: 2599
© 2004 American Society of Clinical Oncology

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Abstract

Enhanced paradoxical type 2 responses generated by interleukin-12 in patients with gastric and colorectal cancer

Nihon University School of Medicine, Tokyo, Japan

2599

Background: Interleukin-12 has been reported to induce type 1 helper T cells (Th1) that produce interleukin (IL)-2 and gamma-interferon (G-IFN), and recognized as one of the strongest immunotherapeutic agent. However, it was found that serum levels of type 2 cytokine such as IL-10 increased after systemic administration of IL-12. Methods: To study this paradoxical phenomenon, peripheral blood mononuclear cells (PBMC) were used collected from 7 healthy volunteer (HV) and 45 patients with gastric and colorectal cancer, and were used for this study. These PBMC were stimulated with IL-12 and the concentrations of É°-IFN, IL-6, IL-10 in the culture supernatant were measured as production of each cytokine after cultivation for 24 hours. Results: The production of IL-6 and IL-10 in patients were significantly higher than in HV. Those of IL-6 by patients with distant metastasis were higher than those by HV. Those of IL-10 were significantly increased in patients with nodal involvement and with distant metastasis than in HV and patients without any metastasis, and these findings were clearer in gastric cancer. Those of IL-6 and IL-10 were significantly correlated each other. Those of G-IFN was increased in patients with nodal involvement and with distant metastasis. Conclusions: Thus IL-12 appeared to induce type 2 responses in patients with cancer and this phenomena may interfere an activation of cell-mediated immunity and may cause an unsuccessful immunotherapy against cancer. A new approach to alter this phenomena is required in order to realize an effective immunotherapy for malignant diseases.

No significant financial relationships to disclose.