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01/22/16 6:49 AM
Thank goodness Peregrine has Dmitry on their side...
Dmitry Gabrilovich : Peregrine Pharmaceuticals KOL :
Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards
Vincenzo Bronte,
Sven Brandau,
Shu-Hsia Chen,
Mario P. Colombo,
Alan B. Frey,
Tim F. Greten,
Susanna Mandruzzato,
Peter J. Murray,
Augusto Ochoa,
Suzanne Ostrand-Rosenberg,
Paulo C. Rodriguez,
Antonio Sica,
Viktor Umansky,
Robert H. Vonderheide &
Dmitry I. Gabrilovich
Nature Communications 7,
Article number:12150 doi:10.1038/ncomms12150
Received
04 November 2015
Accepted
02 June 2016
Published
06 July 2016
Myeloid-derived suppressor cells (MDSCs) have emerged as major regulators of immune responses in cancer and other pathological conditions. In recent years, ample evidence supports key contributions of MDSC to tumour progression through both immune-mediated mechanisms and those not directly associated with immune suppression. MDSC are the subject of intensive research with >500 papers published in 2015 alone. However, the phenotypic, morphological and functional heterogeneity of these cells generates confusion in investigation and analysis of their roles in inflammatory responses. The purpose of this communication is to suggest characterization standards in the burgeoning field of MDSC research.
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Since the inception of this term, interest in MDSC has blossomed. MDSCs are implicated in various aspects of immune regulation in diseases that involve chronic inflammation, especially cancer, but also infection, autoimmune diseases, trauma, graft versus host disease and so on. Recently, evidence of the clinical significance of MDSC in cancer has emerged. Therefore, despite realization that the term ‘MDSC’ may not be optimal, we feel that it is purposeful and should be retained to assure consistency as the field continues to develop.
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These authors contributed equally to this work.
Vincenzo Bronte & Dmitry I. Gabrilovich
Affiliations
Department of Medicine, University Hospital, University of Verona, Verona 37134, Italy
Vincenzo Bronte
Department of Otorhinolaryngology, University Hospital Essen, Essen D-45122, Germany
Sven Brandau
Department of Oncological Sciences, Tisch Cancer Institute, Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA
Shu-Hsia Chen
Department of Experimental Oncology and Molecular Medicine, Molecular Immunology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano 20133, Italy
Mario P. Colombo
New York University School of Medicine, New York, New York 10029, USA
Alan B. Frey
GI-Malignancy Section, Thoracic and GI Oncology Branch, NCI, Bethesda, Maryland 20892, USA
Tim F. Greten
Department of Surgery, Oncology and Gastroenterology, Section of Oncology and Immunology, University of Padova, Padova 35128, Italy
Susanna Mandruzzato
Veneto Institute of Oncology IOV-IRCCS, Padova 35128, Italy
Susanna Mandruzzato
Departments of Infectious Diseases and Immunology, St Jude Children’s Research Hospital, Memphis, Tennessee 38105, USA
Peter J. Murray
Stanley S. Scott Cancer Center, Louisiana State University, New Orleans, Louisiana 70112, USA
Augusto Ochoa
University of Maryland Baltimore County, Baltimore, Maryland 21250, USA
Suzanne Ostrand-Rosenberg
Georgia Regents University Cancer Center, Augusta, Georgia 30912, USA
Paulo C. Rodriguez
Humanitas Clinical and Research Center, Via Manzoni 56, Rozzano, Milan 20089, Italy
Antonio Sica
Department of Pharmaceutical Sciences, Università del Piemonte Orientale ‘Amedeo Avogadro’, via Bovio 6, Novara 20089, Italy
Antonio Sica
Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany
Viktor Umansky
Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim 69120, Germany
Viktor Umansky
Abramson Cancer Center, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
Robert H. Vonderheide
Translational Tumor Immunology, The Wistar Institute, Philadelphia, Pennsylvania 19104, USA
Dmitry I. Gabrilovich
Contributions
V.B. and D.I.G. designed the concept of the review, edited and summarized the contributions of other authors and wrote the paper. S.B., S.-H.C., M.P.C., A.B.F., T.F.G., S.M., P.J.M., A.O., S.O.-R., P.C.R., A.S., V.U. and R.H.V. wrote the paper.
Competing financial interests
The authors declare no competing financial interests.
http://www.nature.com/ncomms/2016/160706/ncomms12150/full/ncomms12150.html
Dmitry Gabrilovich : Peregrine Pharmaceuticals KOL :
Wistar Scientist Sees Many Potential Avenues in MDSC Research
Jane de Lartigue, PhD | October 07, 2016
Dmitry I. Gabrilovich, MD, PhD, concentrates on understanding the role of the tumor microenvironment in the regulation of the immune response in cancer, with a focus on myeloid cells. His research team coined the term myeloid-derived suppressor cell (MDSC) in 2007.
Gabrilovich is the Christopher M. Davis Professor at The Wistar Institute in Philadelphia, a National Cancer Institute-designated cancer center in basic research.
OncLive: How do MDSCs function in normal physiology?
Gabrilovich: MDSCs are pathologically changed immature myeloid cells. Therefore, these cells don’t exist in normal physiology. Cells with the same phenotype in healthy individuals are represented by neutrophils and monocytes.
What is their role in the tumor microenvironment?
It is highly complex. MDSCs cause suppression of various immune cells in the tumor microenvironment, mainly T cells, but also natural killer cells, and B cells. They also aggressively promote tumor angiogenesis, tumor cell invasion, and migration.
What are the most promising potential strategies for targeting MDSCs in cancer therapy?
There are number of ways to target MDSCs. Direct elimination with a specific antibody would be the preferable way, but clinical data are not yet available. Chemotherapeutics like gemcitabine and others can kill MDSCs, but obviously their specificity is very limited. The other ways to target MDSCs include to differentiate these cells or inhibit their production. All-trans retinoic acid was shown to have some effect, and histone deacetylase inhibitors are promising.
A number of other strategies are currently being tested; MDSCs can be also targeted by inhibiting their ability to suppress immune responses. This includes using drugs such as sildenafil, triterpenoids, inhibitors of COX-2, inducible nitric oxide, etc. Migration of MDSCs to the tumor site can be blocked by targeting chemokine receptors, like CXCR2, as well as some chemokines, like IL-8.
What are the most significant unanswered questions relating to the role of MDSCs in cancer?
Better identification of these cells in the blood and tissues of patients with cancer, identification of the methods of their selective targeting, and better understanding of their specific role in the early development of tumors and tumor metastases are all areas that need further research. Large prospective clinical trials to determine the predictive value of these cells in cancer therapy are also needed.
You hosted a conference in June at The Wistar Institute. What would you say was the most exciting aspect of MDSC research discussed there?
The diversity of new ideas was the most striking impression I had. The field is booming with a large number of new investigators bringing fresh ideas to the field. We have learned about new mechanisms of MDSC regulation and targeting, the results of clinical trials indicating their clinical relevance, etc. New technology allows for more precise analysis of the specific contribution of these cells to tumor development.
http://www.onclive.com/publications/oncology-live/2016/vol-17-no-19/wistar-scientist-sees-many-potential-avenues-in-mdsc-research
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