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

It has recently been reported that the CD40-CD40 ligand (CD40L) interaction is important in Th17 development. In addition, transforming growth factor-beta (TGF-ß) 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-ß. Direct CD40-CD40L interaction between MDA-MB231 cells and activated T cells also increased TGF-ß 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-ß production and the differentiation of Th17 cells, which promotes the proliferation of breast cancer cells.

Maturation profiles of peripheral blood dendritic cells in patients with endogenous uveitis.

To determine whether or not maturation of dendritic cells (DCs) is associated with pathogenesis of endogenous uveitis, we analyzed expression of maturation markers, including CD80, CD86, and human leukocyte antigen (HLA)-DR, in peripheral blood (PB) DCs for comparison between healthy controls (HCs) and uveitis patients. A total of 21 patients and 16 HCs were included. Flow cytometric analysis was performed using PB DCs during the active phase of intraocular inflammation. CD86 and HLA-DR expression was higher in PB DCs from uveitis patients versus HCs, whereas that of CD80 was not significantly different. Levels of CD86 and HLA-DR expression tended to parallel those of inflammatory activity, and decreased after anti-inflammatory therapy. However, expression of CD86 and HLA-DR, even in remission, was not completely down-regulated to the low levels found in HCs. Our results indicate the maturation of DCs may play a role in the pathogenesis of endogenous uveitis. The relatively high expression of HLA-DR and co-stimulatory molecules even in the quiescence of inflammation suggests maturation of DCs may be associated with chronicity and recurrence of uveitis.

Identification of CM1 as a Pathogenic Factor in Inflammatory Diseases and Cancer.

BACKGROUND: CM1 (centrocyte/-blast marker 1) was defined by a mAb against concanavalin A (Con A) activated PBMC. It is expressed in germinal center of human tonsil and on the surface of activated PBMC as well as cancer cells. Recently, increased productions of pro-inflammatory mediators were detected from activated PBMC by CM1 ligation. METHODS: However, there is a limitation to explain the exact role of CM1 on inflammation and its related mechanisms, since the identity of CM1 is still not clarified. In our previous study, we have already confirmed that soluble form of CM1 was produced by Raji. Therefore, we performed Q-TOF analysis after immunoprecipitation of concentrated Raji culture supernatant using anti-CM1 mAbs. RESULTS: As a result, we found that CM1 is identical to enolase-1(ENO1), a glycolytic enzyme, and we confirmed that results by silencing ENO1 using siRNA. It was also confirmed through competition assay between anti-CM1 and anti-ENO1 mAbs. Finally, we investigated the possible role of CM1 in inflammatory response and cancer. The ligation of CM1 on Raji cells with anti-CM1 mAbs induces the extensive production of prostaglandin E(2)(PGE(2)). In addition, the increased activity of matrix metalloproteinase (MMP)-2/9 was shown in NCI-N87, stomach cancer cell line by CM1 stimulation. CONCLUSION: CM1 is identical to ENO1 and it might be an important role in the regulation of inflammatory responses.