Expression of CD40 Ligand in CD40-positive Murine Tumors Activates Transcription of the Interleukin-23 Subunit Genes and Produces Antitumor Responses

Abstract

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.