Expression of CD40 ligand in CD40-positive murine tumors activates transcription of the interleukin-23 subunit genes and produces antitumor responses

Anticancer Res. 2004 Sep-Oct;24(5A):2713-6.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD40 Antigens / biosynthesis
  • CD40 Ligand / biosynthesis*
  • CD40 Ligand / genetics
  • CD40 Ligand / immunology
  • Carcinoma, Lewis Lung / genetics
  • Carcinoma, Lewis Lung / immunology*
  • Carcinoma, Lewis Lung / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Interleukin-12 / biosynthesis*
  • Interleukin-12 / genetics
  • Interleukin-12 Subunit p40
  • Interleukin-23
  • Interleukin-23 Subunit p19
  • Interleukins / biosynthesis*
  • Interleukins / genetics
  • Lung Neoplasms / genetics
  • Lung Neoplasms / immunology*
  • Lung Neoplasms / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Protein Subunits / biosynthesis*
  • Protein Subunits / genetics
  • Transcription, Genetic
  • Transfection
  • Up-Regulation

Substances

  • CD40 Antigens
  • Il23a protein, mouse
  • Interleukin-12 Subunit p40
  • Interleukin-23
  • Interleukin-23 Subunit p19
  • Interleukins
  • Protein Subunits
  • CD40 Ligand
  • Interleukin-12