Vaccination effect of interleukin-6-producing pancreatic cancer cells in nude mice: a model of tumor prevention and treatment in immune-compromised patients.
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.
Yano
T
T
Department of Pathology, Hokkaido University School of Medicine, Kita-ku, Sapporo 060-8638, Japan.
Ishikura
H
H
Kato
H
H
Ogawa
Y
Y
Kondo
S
S
Kato
H
H
Yoshiki
T
T
D000818:Animals; D000912:Antibodies, Neoplasm / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D000918:Antibody Specificity; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis / Q000276:immunology*; D015850:Interleukin-6 / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000276:immunology* / Q000517:prevention & control; D013997:Time Factors; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000912:Antibodies, Neoplasm; D019496:Cancer Vaccines; D007074:Immunoglobulin G; D015850:Interleukin-6