Copyright © 2015 Massachusetts Medical Society. BACKGROUND Crohn’s disease–related inflammation is characterized by reduced activity of the immunosuppressive cytokine transforming growth factor β1 (TGF-β1) due to high levels of SMAD7, an inhibitor of TGF-β1 signaling. Preclinical studies and a phase 1 study have shown that an oral SMAD7 antisense oligonucleotide, mongersen, targets ileal and co...

Myeloid-derived suppressor cells (MDSCs) promote tumor growth and metastasis. We have recently demonstrated that the pro-inflammatory cytokine macrophage migration inhibitory factor (MIF) enhances the immunosuppressive microenvironment by increasing the abundance of monocytic MDSCs within the tumor. Our results suggest that MIF is a potential therapeutic target for the prevention of metastasis ...

The development of therapeutic cancer vaccines is impacted by immunosuppressive elements in the tumor microenvironment. Most immunogenic cancer proteins are "self," therefore, peripheral tolerance contributes substantially to tumor immune escape. Transforming growth factor beta (TGFbeta) actively modulates both inflammation and tolerance induction. Combining vaccination with agents that disarm ...

In the past, the transcription factor STAT1 was considered as a tumor suppressor. We have recently discovered that STAT1 in malignant cells favors breast cancer progression as it stimulates immunosuppressive effects mediated by myeloid-derived suppressor cells (MDSCs). Inhibiting STAT1 activity offers a promising therapeutic approach against advanced breast cancer.

The induction of antitumor immune responses by dendritic cell (DC)/tumor cell fusions can be modulated by their activation status. Our recent work reveals that the combination of Toll-like receptor 2 (TLR2) and TLR4 agonists promotes the immunogenicity of DC/tumor cell fusions, allowing them to overcome the immunosuppressive effects of transforming growth factor β1.

More than thirty patients have now undergone liver transplantation in Denver, some more than once, and survivals of up to two and a half years have been achieved. Through this and other experience it has been learned that graft viability is more critical than histocompatibility matching but that the most important factor in the ultimate outcome is prevention of rejection through vigorous immuno...