Vaccination Effect of Interleukin-6-producing Pancreatic Cancer Cells in Nude Mice: A Model of Tumor Prevention and Treatment in Immune-compromised Patients |
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Authors: | Tomoyuki Yano Hiroshi Ishikura Hiroaki Kato Yayoi Ogawa Satoshi Kondo Hiroyuki Kato Takashi Yoshiki |
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Affiliation: | Department of Pathology, Hokkaido University School of Medicine, Kita-15 Nishi-7, Kita-ku, Sapporo 060-8638;Department of Surgery, Hokkaido University School of Medicine, Kita-15 Nishi-7, Kita-ku, Sapporo 060-8638 |
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Abstract: | In an effort to explore properties important in hematogenous metastasis of pancreatic adenocarcinoma, we previously demonstrated that tumor-derived interleukin (IL)-6 is a crucial factor that conveys resistance to liver metastasis. Here we extend the study to examine a possible vaccination effect of tumor-derived IL-6 in T-cell-deficient nude mice, as a model for predicting the effect in immune-compromised patients. We used a pair of IL-6-nonproducing and highly producing pancreatic adenocarcinoma cell lines, PCI-43 and PCI-43h, respectively. The reaction intensity of anti-PCI IgG antibodies in host nude mice was maximal 28 days after inoculation of PCI-43h cells, and remained high thereafter. A fraction of the pancreatic carcinoma cell lines, namely, PCI-6, -10, and -43, expressed surface antigenic determinant(s) reactive with the IgG; but the others, PCI-19, -24, -55, -64, -66, -68, -72, and -79, did not. Inoculation of PCI-43h but not PCI-43 suppressed growth of simultaneously inoculated PCI-43, but not PCI-24 xenografts. In addition, administration of PCI-43h, but not PCI-43 suppressed the growth of PCI-43 that was xenografted 4 weeks later, thus revealing a vaccination effect of IL-6-producing PCI-43h, but not IL-6-nonproducing PCI-43. These data, obtained from T-cell-deficient nude mice, suggest an in vivo role for IL-6 in inducing IgG-mediated, pancreatic carcinoma-specific vaccination against a thymus-independent antigen. |
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Keywords: | Pancreatic carcinoma IL-6 Vaccination Anti-tumor immunity |
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