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.
Highlights
CD40 is a 50 kDa type I transmembrane protein that belongs to the tumor necrosis factor (TNF)-receptor superfamily [1]
Because CD40 stimulation is known as a critical factor in the proliferation and differentiation of B cells [33], whether the proliferation of MDA-MB231 cells is increased by stimulation of CD40 with anti-CD40 antibody was investigated
CD40 is mainly expressed on antigen presenting cells (APCs) including B cells, dendritic cells, and macrophages to activate immune responses after interaction with its ligand, CD40 ligand (CD40L), on activated T cells [39,40,41]
Summary
CD40 is a 50 kDa type I transmembrane protein that belongs to the tumor necrosis factor (TNF)-receptor superfamily [1]. It is physiologically expressed in various cell types including dendritic cells, B cells and monocytes/macrophages [2]. CD40 in B cells has a critical role in the development and proliferation of B cells by enhancing interleukin (IL)-2, IL-4, and IL-5 and the production of other chemokines. The ligand for CD40 is CD154 (CD40L) which is predominantly expressed in activated T cells and has a crucial role in the regulation of B cell proliferation [9, 10]. In addition to B cells, CD40 is expressed in several kinds of PLOS ONE | DOI:10.1371/journal.pone.0125742 May 18, 2015
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