Expression of CD40 ligand in CD40-positive murine tumors activates transcription of the interleukin-23 subunit genes and produces antitumor responses.
CD40-positive dendritic cells (DCs) are stimulated with CD40 ligand (CD40L) and subsequently secrete a number of cytokines including interleukin (IL)-23, which is involved in cell-mediated immune responses. Expression of CD40 ligand (CD40L) on tumors can activate host immune systems and produce antitumor effects against the tumors. We examined a possible mechanism of the antitumor responses: tumor cells expressing CD40 can transcribe DCs-derived cytokine genes by the expressed CD40L. For the purpose, CD40-positive A11 and -negative P29 murine lung tumors cells, both of the same origin, were transfected with the CD40L gene (A11/CD40L and P29/CD40L). The growth rate in vitro of A11/CD40L and P29/CD40L cells was not different from that of the respective parent tumors; however, the growth in vivo of A11/CD40L tumors in syngeneic mice was significantly retarded and the growth retardation of P29/CD40L tumors was marginaL Transcription of the p40 and p19 genes, IL-23 subunit genes, was up-regulated in A11/CD40L cells compared with parent A11 cells, whereas this up-regulation was not observed in P29/CD40L cells. Since expression of IL-23 in tumors can produce antitumor effects, the present data suggest that the CD40/CD40L interaction can activate cytokine transcripts in certain tumors and consequently contribute to antitumor responses.
Wada
Akihiko
A
Division of Pathology, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuo-ku, Chiba, Japan.
Tada
Yuji
Y
Shimozato
Osamu
O
Takiguchi
Yuichi
Y
Tatsumi
Koichiro
K
Kuriyama
Takayuki
T
Tagawa
Masatoshi
M
D000818:Animals; D019013:CD40 Antigens / Q000096:biosynthesis; D023201:CD40 Ligand / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D018827:Carcinoma, Lewis Lung / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000235:genetics; D053762:Interleukin-12 Subunit p40; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins / Q000096:biosynthesis* / Q000235:genetics; D008175:Lung Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D021122:Protein Subunits / Q000096:biosynthesis* / Q000235:genetics; D014158:Transcription, Genetic; D014162:Transfection; D015854:Up-Regulation
D019013:CD40 Antigens; C508841:Il23a protein, mouse; D053762:Interleukin-12 Subunit p40; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins; D021122:Protein Subunits; D023201:CD40 Ligand; D018664:Interleukin-12