Role for CD40-CD40 ligand interactions in the immune response to solid tumours

Anton B. Alexandroff, Andrew M. Jackson, T. Paterson, Joanne L. Haley, James A. Ross, D. L. Longo, William J Murphy, Keith James, Dennis D. Taub

Research output: Contribution to journalArticle

71 Scopus citations

Abstract

CD40-mediated interactions play an important role in the response to infections, transplantation, and cancer by affecting the development, activation, proliferation and differentiation of a variety of immune cells. In the current study we examined the role of CD40-mediated interactions in immune responses to bladder, pancreatic and breast carcinomas as well as melanoma cell lines using soluble human CD40L (rhCD40L) or anti-CD40 mAb in vitro. CD40 expression was readily detected in a large proportion of the cell lines and was augmented but not induced de novo by treatment with IFNγ. Treatment of CD40-positive cell lines with rhCD40L or anti-CD40mAb enhanced cell surface expression of ICAM-1 and FAS and stimulated the production of IL-6, IL-8, GROα, GM-CSF and TNFα but not IL-4, IL-10, TGFβ, MCP-1, RANTES, MIP-1β, or IP-10. In addition, incubation of CD40 + tumour cell lines with immobilised rhCD40L or anti-CD40 mAb in vitro resulted in significant inhibition of proliferation and a corresponding decrease in viability. This CD40-mediated inhibition of cell growth was due, at least in part, to alterations in cell cycle and the induction of apoptosis. Transfection of CD40-negative tumour cell lines with the cDNA for CD40 conferred responsiveness to rhCD40L and anti-CD40 antibody. Finally, the presence of CD40 on the surface of carcinoma lines was found to be an important factor in the generation of tumour-specific T cell responses. (C) 2000 Elsevier Science Ltd.

Original languageEnglish (US)
Pages (from-to)515-526
Number of pages12
JournalMolecular Immunology
Volume37
Issue number9
DOIs
StatePublished - 2000
Externally publishedYes

Keywords

  • Apoptosis
  • Carcinoma
  • CD40
  • CD40-ligand
  • Melanoma
  • T-lymphocyte

ASJC Scopus subject areas

  • Molecular Biology
  • Immunology

Fingerprint Dive into the research topics of 'Role for CD40-CD40 ligand interactions in the immune response to solid tumours'. Together they form a unique fingerprint.

  • Cite this

    Alexandroff, A. B., Jackson, A. M., Paterson, T., Haley, J. L., Ross, J. A., Longo, D. L., Murphy, W. J., James, K., & Taub, D. D. (2000). Role for CD40-CD40 ligand interactions in the immune response to solid tumours. Molecular Immunology, 37(9), 515-526. https://doi.org/10.1016/S0161-5890(00)00079-1