Protective immunity is induced in murine colon carcinoma cells by the expression of interleukin-12 or interleukin-18, which activate type 1 helper T cells.
We investigated the antitumor effects induced by the production of interleukin-12 (IL-12) or IL-18, which influence the function of T helper type 1 cells, in murine colon carcinoma cells (Colon 26). Retrovirally transduced cells with IL-12 genes that encoded both p35 and p40 (Colon 26/IL-12) lost their tumorigenicity when inoculated subcutaneously or intraperitoneally into syngeneic immunocompetent mice. Moreover, the mice that had rejected the Colon 26/IL-12 cells generated protective immunity to wild-type (wt) cells when subsequently challenged. Colon 26 cells transduced with the IL-18 gene (Colon 26/IL-18) could not form subcutaneous tumors in immunocompetent mice, and the mice became resistant to inoculated wt cells. Immunohistochemical analysis revealed that the numbers of blood vessels in Colon 26/IL-12 or Colon 26/IL-18 tumors were markedly reduced, and that the expression of adhesion molecules such as intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 increased on the endothelium in the stroma of Colon 26/IL-12 tumors. The loss of tumorigenicity of Colon 26/IL-12 or Colon 26/IL-18 cells was not observed in immunocompromised mice. However, the survival days of the immunocompromised mice inoculated with Colon 26/IL-12 but not Colon 26/IL-18 cells were significantly longer than those inoculated with wt cells. The secretion of cytokines that stimulate T helper type 1 cells from tumor cells can thereby induce an antitumor response. However, the effector cells involved in these antitumor effects could differentially migrate to the tumors, and the inhibition of angiogenesis may partially contribute to the antitumor responses observed.
Tasaki
K
K
Department of Surgery (II), Chiba University School of Medicine, Japan.
Yoshida
Y
Y
Maeda
T
T
Miyauchi
M
M
Kawamura
K
K
Takenaga
K
K
Yamamoto
H
H
Kouzu
T
T
Asano
T
T
Ochiai
T
T
Sakiyama
S
S
Tagawa
M
M
D000818:Animals; D003110:Colonic Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control*; D005260:Female; D007110:Immunity, Active; D016867:Immunocompromised Host / Q000276:immunology; D007150:Immunohistochemistry; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D020382:Interleukin-18 / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism* / Q000637:transplantation; D014407:Tumor Cells, Cultured / Q000637:transplantation
D020382:Interleukin-18; D018664:Interleukin-12