Direct Interaction of CD40 on Tumor Cells with CD40L on T Cells Increases the Proliferation of Tumor Cells by Enhancing TGF-β Production and Th17 Differentiation

PLoS One. 2015 May 18;10(5):e0125742. doi: 10.1371/journal.pone.0125742. eCollection 2015.

Abstract

It has recently been reported that the CD40-CD40 ligand (CD40L) interaction is important in Th17 development. In addition, transforming growth factor-beta (TGF-β) promotes tumorigenesis as an immunosuppressive cytokine and is crucial in the development of Th17 cells. This study investigated the role of CD40 in breast cancer cells and its role in immunosuppressive function and tumor progression. CD40 was highly expressed in the breast cancer cell line MDA-MB231, and its stimulation with CD40 antibodies caused the up-regulation of TGF-β. Direct CD40-CD40L interaction between MDA-MB231 cells and activated T cells also increased TGF-β production and induced the production of IL-17, which accelerated the proliferation of MDA-MB231 cells through the activation of STAT3. Taken together, the direct CD40-CD40L interaction of breast tumor cells and activated T cells increases TGF-β production and the differentiation of Th17 cells, which promotes the proliferation of breast cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / genetics
  • Breast Neoplasms / immunology*
  • Breast Neoplasms / pathology*
  • CD40 Antigens / antagonists & inhibitors
  • CD40 Antigens / genetics
  • CD40 Antigens / metabolism*
  • CD40 Ligand / metabolism*
  • Cell Differentiation
  • Cell Line, Tumor
  • Cell Proliferation
  • Coculture Techniques
  • Female
  • Humans
  • Interleukin-17 / metabolism
  • Lymphocyte Activation
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism
  • RNA, Small Interfering / genetics
  • STAT3 Transcription Factor / metabolism
  • T-Lymphocytes / immunology*
  • Th17 Cells / immunology*
  • Th17 Cells / pathology
  • Transforming Growth Factor beta / biosynthesis*
  • Transforming Growth Factor beta / genetics
  • Up-Regulation

Substances

  • CD40 Antigens
  • Interleukin-17
  • RNA, Messenger
  • RNA, Neoplasm
  • RNA, Small Interfering
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Transforming Growth Factor beta
  • CD40 Ligand

Grant support

Grant from the National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea (#1020030).