Tumor-derived interleukin (IL)-6 induced anti-tumor effect in immune-compromised hosts.
Tumor-derived cytokines, such as interleukin (IL)-6, function in the context of tumor-to-host interactions, and their functions in immune-compromised hosts need to be addressed in the light of ever- increasing number of patients under immunosuppression. We studied the effects, in immune-comprised animals, of tumor-derived IL-6 on tumor growth using an experimental tumor vaccination model. Murine mammary carcinoma FM3A clone 25 (CL25) cells, which neither produce IL-6 nor express IL-6 receptors, were used. cDNA for murine IL-6 (mIL-6) was introduced to the CL25 cells, resulting in a high-producer (mIL-6H) clone. In the severe combined immune-deficient (SCID) mice, the inoculation 3 weeks earlier of mIL-6H to a dorsal flank site suppressed the growth of the CL25 cells at the opposite flank site; a tumor-derived IL-6-mediated vaccination effect occurred. In the T-cell-deficient nude mice, the inoculations 4 weeks earlier of mIL-6H suppressed the growth of CL25, but the simultaneous inoculation of these transfectants did not affect the growth of CL25. Reducing the number of inoculated transfectants or a shorter vaccination period obscured the suppressive effect. The amounts of circulating tumor-reactive immunoglobulin did not correlate with the suppressive effect. The subcutaneous injection of the anti-CD40 antibody generated a further suppression of tumor growth in the mIL-6H-inoculated, but not in the mock-inoculated, T-cell-deficient mice. In the immune-competent hosts, a suppressive effect was not observed. Natural killer (NK) activity was augmented in the spleen of mIL-6H-inoculated scid mice. This study indicated a possible vaccination effect with tumor-derived IL-6 in immune-compromised hosts.
Ishiguro
Hiroshi
H
Department of Molecular Pathology, Chiba University Graduate School of Medicine, Inohana 1-8-1, Chuo-ku, Chiba 260-8670, Japan.
Kishimoto
Takashi
T
Furuya
Mitsuko
M
Nagai
Yuichiro
Y
Watanabe
Toru
T
Ishikura
Hiroshi
H
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage; D000912:Antibodies, Neoplasm / Q000097:blood; D019013:CD40 Antigens / Q000276:immunology; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy / Q000276:immunology; D045744:Cell Line, Tumor; D017690:Cell Transplantation; D018076:DNA, Complementary / Q000235:genetics; D016867:Immunocompromised Host; D007136:Immunoglobulins / Q000097:blood; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics*; D007694:Killer Cells, Natural / Q000276:immunology; D015674:Mammary Neoplasms, Animal / Q000188:drug therapy* / Q000276:immunology; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection
D000906:Antibodies; D000912:Antibodies, Neoplasm; D019013:CD40 Antigens; D019496:Cancer Vaccines; D018076:DNA, Complementary; D007136:Immunoglobulins; D015850:Interleukin-6