Dhaval Yohita just posted this youtube video below, well.. its a 49 second silent film of sorts, but the 5 facts are listed below from the youtube clip
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FACTS: (from within the youtube clip..)
1) Reciprocal relationship between MDSC's and T-cells
2) Youn JI, Kumar V, Collazo M, Nefedova Y, Condamine T, Cheng P, Villagra A, Antonia S, McCaffrey JC, Fishman M, Sarnaik A, Horna P, Sotomayor E, Gabrilovich DI.
3) Epigenetic silencing of retinoblastoma gene regulates pathologic differentiation of myeloid cells in cancer
4) Condamine T, Kumar V, Ramachandran IR, Youn JI, Celis E, Finnberg N, El-Deiry WS, Winograd R, Vonderheide RH, English NR, Knight SC, Yagita H, McCaffrey JC, Antonia S, Hockstein N, Witt R, Masters G, Bauer T, Gabrilovich DI.
5) ER Stress regulates MDSC cate through TRAIL-R-mediates apoptosis
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Fact#2 cites from #13 below.. Fact#4 cites from #19 below..
Thank goodness Peregrine has Dmitry on their side...
Summary
The laboratory of Dmitry Gabrilovich focuses on understanding of the role of tumor microenvironment in regulation of immune responses in cancer and tumor progression with specific emphasis on meyloid cells. Based on advances in basic research in the lab they develop new methods of cancer therapy.
Myeloid cells play a major role in regulation of immune responses. They include professional antigen-presenting cells, dendritic cells (DC), macrophages and myeloid-derived suppressor cells. Data generated in his laboratory have demonstrated that differentiation and function of various myeloid cells in caner is severely affected. Gabrilovich and his team was one of the first who identified the phenomenon of abnormal regulation of DC differentiation and cancer and described the mechanisms regulating this phenomenon. They proposed several therapeutic strategies to overcome those defects. Some of them are currently being tested in clinical trials.
Gabrilovich and his group have found that defects in differentiation of DC are associated with accumulation of immature myeloid cells in tumor-bearing animals and patients with cancer. Under normal conditions, these cells represent an intermediate stage of myeloid cell differentiation. In cancer, however, they lose the ability to differentiate into mature myeloid cells, including granulocytes, DC, and macrophages. They become functionally defective and acquire the ability to suppress immune responses. Gabrilovich together with investigators from other institutions coined the term “myeloid-derived suppressor cells (MDSC)” which is now widely used to characterize these cells. Since 2007, when the term was introduced by Gabrilovich and colleagues, more than 2200 papers studying these cells were published.
His lab looks at different aspects of immature myeloid cell biology in cancer. First, they are trying to understand the signaling pathways that are responsible for accumulation and functional defects of immature myeloid cells in cancer. These pathways include NF-kB, Jak-STAT, Notch, Wnt, Rb, and others. Second, they are investigating cellular and molecular mechanisms of T-cell suppression and tolerance induced as a result of abnormal differentiation of myeloid cells and abnormal DC function. The main focus of this group is on the role of reactive oxygen species and peroxynitrite in regulation of T-cell function. His work demonstrates that reactive oxygen species produced by immature myeloid cells in vitro and in tumor-bearing animals in the presence of tumor-derived soluble factors are substantial contributors to the immunosuppression mediated by these cells in cancer. In recent years Dr. Gabrilovich is focused on the role of lipid accumulation in the defective function of DCs and MDSC in cancer as well as on the mechanisms regulating MDSC migration to form pre-metastatic niche and activate dormant tumor cells.
Gabrilovich and his groups also investigate new immune therapy strategies in cancer. They are exploring several different approaches, including genetically modified DCs, T-cell transfers, checkpoint blockade, and others. In recent years the focus of the lab on the emerging new paradigm of combining conventional chemotherapy, radiation therapy, and immunotherapy.
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