Multimodality treatment of intrahepatic cholangiocarcinoma: A review.

Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary hepatic cancer in the United States. Currently, curative treatment involves aggressive surgery. Chemotherapy and radiation treatments have been used for unresectable tumors with some success.

Novel sphingosine-1-phosphate receptor modulator KRP203 combined with locally delivered regulatory T cells induces permanent acceptance of pancreatic islet allografts.

Background: KRP203, a structural FTY720 analogue, has 5-fold greater selectivity for binding to sphingosine-1-phosphate receptor (S1PR) 1 (S1PR(1)) versus S1PR3 and 100-fold greater selectivity over S1PR(2) and S1PR(5). Although the immunoregulatory effects of FTY720 have been tested in clinical and experimental research, the therapeutic efficacy of KRP203 in allograft models remains elusive. In this study, we investigated the potential of KRP203 alone and in combination with intragraft injection of CD4(+)CD25(+)FoxP3(+) regulatory T cells (Tregs) to induce islet allograft tolerance.

Anti-TCRβ mAb induces long-term allograft survival by reducing antigen-reactive T cells and sparing regulatory T cells.

TCR specific antibodies may modulate the TCR engagement with antigen-MHC complexes, and in turn regulate in vivo T cell responses to alloantigens. Herein, we found that in vivo administration of mAbs specific for mouse TCRβ (H57-597), TCRα or CD3 promptly reduced the number of CD4(+) and CD8(+) T cells in normal mice, but H57-597 mAb most potently increased the frequency of CD4(+) Foxp3(+) Treg cells. When mice were injected with staphylococcal enterotoxin B (SEB) superantigen and H57-597 mAb, the expansion of SEB-reactive Vβ8(+) T cells was completely abrogated while SEB-nonreactive Vβ2(+) T cells remained unaffected.

IL-7, but not thymic stromal lymphopoietin (TSLP), during priming enhances the generation of memory CD4+ T cells.

Multiple activation signals (including antigen, co-stimulation, and cytokines) during T-cell priming affect the subsequent generation of memory T cells, whose survival is maintained by IL-7 and IL-15. Since the IL-7 receptor is highly expressed not only on the surface of memory T cells but also on naïve T cells, we propose that early exposure to IL-7 during priming of naïve T cells may promote their survival, and thus enhances the generation of memory cells. To test this hypothesis, TCR transgenic OT-II CD4(+) T cells were stimulated in vitro with OVA(323-339) peptide presented by syngeneic antigen-presenting cells (APCs).