Suzanne Ostrand-Rosenberg
Prof. Biology, Robert+Jane Meyerhoff Chair
| Phone |
410-455-2237
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|---|---|
| srosenbe@umbc.edu | |
| Education |
Ph D, California Institute of Technology (1975)
Other, Barnard College, Columbia University (1970)
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| CV | View CV |
About
I have more than 37 years of experience as the PI of a laboratory studying the immune system’s response to malignancies. Throughout this period my lab’s long-term goal has been to manipulate an individual's immune response to reject cancer cells. In the 1990’s we were instrumental in demonstrating that CD4+ T helper lymphocytes are essential for immune-mediated tumor rejection. Recently, we were among the first labs to appreciate that myeloid-derived suppressor cells (MDSC) are highly immune suppressive cells present in virtually all cancer patients, and are a significant obstacle to active cancer immunotherapies. Our work demonstrating that MDSC are induced by a variety of pro-inflammatory mediators was described in a Science Magazine “News Focus” article and is the basis for the concept that chronic inflammation increases cancer risk and cancer progression by inducing MDSC which inhibit anti-tumor immunity. Our lab was also the first to demonstrate that macrophages, the other major pro-tumor myeloid cell population that infiltrates solid tumors, undergo cross-talk with MDSC which enhances the pro-tumor activity of both cell populations. Studies to date have identified a variety of physiological conditions and molecules that drive the accumulation and suppressive potency of MDSC and macrophages. However, neutralization of these cells has been unsuccessful because of the multiple pro-inflammatory mediators that drive their accumulation and function. Our preliminary studies, which are the basis for this application, demonstrate that the ubiquitously expressed alarmin, HMGB1, and the pro-inflammatory mediator S100A8/A9, are master regulators that activate MDSC by binding to the Receptor for Advanced Glycation Endproducts (RAGE). These observations led us to hypothesize that pro-tumor MDSC and TAMs may be neutralized by targeting RAGE, HMGB1, and S100A8/A9. If our hypothesis is correct, then our studies will provide a global and universal strategy for eliminating the suppressive activity of these myeloid cell populations and provide a more favorable environment for immunotherapy in cancer patients.
Research Interests
Tumor/cancer immunology; tumor-induced immune suppression; cancer vaccine development
Teaching Interests
Immunology Cell Biology Cancer Biology
Selected Classes
| Spring 2014 | BIOL 397 – Ethics and Integrity in Scientific Research |
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Contracts, Fellowships, Grants, and Sponsored Research
Mechanisms of trans-cell action of tumor suppressors expressed in myeloid cells Grant (Currently Under Review) Sponsored by NIH (Sep 1, 2018)
A novel BiTE as an immunotherapy drug for the treatment of cancer Grant (Funded) Sponsored by TEDCO MII program (Sep 28, 2015 – Jun 28, 2016)
Targeting the COX-2 Pathway to Reduce Breast Cancer Mortality Grant (Funded) Sponsored by VA (UMB subcontract to UMBC) (Jun 1, 2015 – May 30, 2019)
A novel recombinant molecule that simultaneously inhibits PDL1/PD1-mediated immune suppression and boosts the activation of tumor-reactive T cells. Cooperative Agreement (Funded) Sponsored by MedImmune, Inc. (Sep 3, 2014 – Jun 2, 2016)
Does G-CSF promote maternal-fetal tolerance by inducing immune suppressive myeloid-derived suppresser cells (MDSC)? Cooperative Agreement (Funded) Sponsored by Nora Therapeutics (Apr 23, 2014 – Apr 22, 2015)
Ubiquitinated Proteins in Exosomes of Immune Suppressive Myeloid Cells. Grant (Funded) Sponsored by NIH (Feb 1, 2014 – Jun 30, 2018)
Amplifying TCR Responses and Resisting MDSC-mediated Suppression via MyD88 Signaling in T cells Grant (Not Funded) Sponsored by NIH
Intellectual Contributions
(2018) Myeloid derived-suppressor cells: their role in cancer and obesity Current Opinion in Immunology Download.
(2018) Differential Content of Proteins, mRNAs, and miRNAs Suggests that MDSC and Their Exosomes May Mediate Distinct Immune Suppressive Functions American Society of Biological Chemistry Journal of Proteome Research Download.
(2018) Myeloid-Derived Suppressor Cells: Immune-Suppressive Cells That Impair Antitumor Immunity and Are Sculpted by Their Environment American Association of Immunologists Journal of Immunology Download.
(2018) Ubiquitin Conjugation Probed by Inflammation in Myeloid-Derived Suppressor Cell Extracellular Vesicles American Society of Biological Chemistry Journal of Proteome Research Download.
(2018) Soluble CD80 protein delays tumor growth and promotes tumor infiltrating lymphocytes American Association of Cancer Research Cancer Immunology Research Download.
(2017) CD3xPDL1 bi-specific T cell engager (BiTE) simultaneously activates T cells and kills PDL1+ tumor cells Oncotarget
(2016) Frontline Science: Myeloid-derived suppressor cells (MDSCs) facilitate maternal-fetal tolerance in mice Society of Leukocyte Biology Journal of Leukocyte Biology
(2016) Tumor-induced MDSC act via remote control to inhibit L-selectin-dependent adaptive immunity in lymph nodes eLIFE
(2016) Myeloid-derived suppressor cells. Encyclopedia of Immunobiology Oxford Academic Press Elsevier
(2016) Myeloid-Derived Suppressor Cell Survival and Function Are Regulated by the Transcription Factor Nrf2 American Association of Immunologists Journal of Immunology
(2016) High-mobility group box protein 1 promotes the survival of myeloid-derived suppressor cells by inducing autophagy Society of Leukocyte Biology Journal of Leukocyte Biology
(2016) Tolerance and immune suppression in the tumor microenvironment Elsevier Cellular Immunology
(2015) Myeloid-derived suppressor cells: critical cells driving immune suppression in the tumor microenvironment Advances in Cancer Research Advances in Cancer Research
(2015) Novel strategies for inhibiting PD-1 pathway-mediated immune suppression while simultaneously delivering activating signals to tumor-reactive T cells Springer, Cancer Immunology, Immunotherapy
(2015) Top-down analysis of low mass proteins in exosomes shed by murine myeloid-derived suppressor cells. International Journal of Mass Spectrometry
(2014) Ubiquitinated proteins in exosomes secreted by myeloid-derived suppressor cells Journal of Proteome Research
(2014) The programmed death-1 immune-suppressive pathway: barrier to antitumor immunity American Association of Immunologists The Journal of Immunology
(2014) Cross-talk among myeloid-derived suppressor cells, macrophages, and tumor cells impacts the inflammatory milieu of solid tumors Society of Leukocyte Biology Journal of Leukocyte Biology
(2014) Exosomes from myeloid-derived suppressor cells carry biologically active proteins American Chemical Society J. Proteome Research
(2014) Macrophages and tumor development Tumor-Induced Immune Suppression - Mechanisms and Therapeutic Reversal NY, Heidelberg,Dordrecht, London Springer
(2013) Soluble CD80 Restores T cell Activation and overcomes tumor cell programmed death ligand 1-mediated immune suppression. J. of Immunology
(2013) Myeloid‑derived suppressor cell function is reduced by Withaferin A, a potent and abundant component of Withania somnifera root extract NY, Heidelberg,Dordrecht, London Springer
(2013) Inflammation, Tumor Progression, and Immune Suppression Tumor Immunoenvironment NY, Heidelberg,Dordrecht, London Springer
(2013) Looking to the future of cancer immunotherapy: many questions to answer and many therapeutic opportunities Berlin-Heidelberg Springer-Verlag
Understanding the Tumor Immune Microenvironment (TIME) for effective therapy springer/Nature Nature Medicine
Immune suppressive myeloid-derived suppressor cells in cancer Encyclopedia of Immunology Elsevier
Intellectual Property
Patent Recombinant Bi-specific Polypeptides for Coordinately Activating Tumor-reative T Cells and Neutralizing Immune Suppression 62092506 (application number) Application: Dec 16, 2014
Patent Solulble CD80 as a therapeutic to reverse immune suppression in cancer patients 13/660,037 Submitted: Oct 25, 2011 Application: Oct 25, 2012 Approved: Dec 5, 2014
Research in Progress
Myeloid-derived suppressor cells (MDSC) promote tumor progression and weight gain, but protect against metabolic dysfunction in obese mice Scholarly (On-Going) Mar 1, 2015
Presentations
1st European Symposium on Myeloid Regulatory Cells in Health and Disease Lecture Mye-EUNITER Essen, Germany (Nov 1, 2018)
Infection and Immunity Research Forum (IIRF) Annual conference Keynote/Plenary Address IIRF Western University, London, Ontario Canada (Oct 11, 2018)
Progress in Vaccination Against Cancer 18 Lecture PIVAC 18 Oslo, Norway (Oct 3, 2018)
Frontiers in Molecular Oncology International Conference Keynote/Plenary Address Myeloid-derived suppressor cells: Potent immune suppressors in the tumor microenvironment Universidade Estadual Paulista Sao Paulo, Brazil (Jun 9, 2018)
American Association of Immunologists Annual conference Lecture Writing Scientific Manuscripts and Responding to Reviewers American Association of Immunologists Austin, TX (May 6, 2018)
Cold Spring Harbor Symposium on Tumor Immunology & Immunotherapy Lecture Immune suppression in obesity and tumor progression Cold Spring Harbor Suzhou, China (Oct 22, 2017)
Progress in Vaccination Against Cancer , 17th edition Keynote/Plenary Address The good, the bad, and the in-between: immune suppression, obesity, and tumor progression PIVAC (Progress in Vaccination Against Cancer) Loutraki, Greece (Sep 26, 2017)
47th Annual meeting of the German Society for Immunology Lecture Obesity, immune suppression, & tumor progression German Society for Immuno9logy Erlangen, Germany (Sep 13, 2017)
22nd Congress of the European Hematology Association Lecture Myeloid-derived suppressor cells (MDSC): Critical cells that link obesity to cancer and drive immune suppression in the tumor microenvironment European Hematology Association Madrid, Spain (Jun 22, 2017)
American Association of Immunologists annual meeting 2017 Keynote/Plenary Address The good, the bad, and the in-between: immune suppression, obesity, and tumor progression American Association of Immunologists Washington, DC (May 12, 2017)
II congreso Internacional de Immuno-Oncologia Keynote/Plenary Address Understanding and neutralizing cancer-induced immune suppression to promote antitumor immunity Mexican National Cancer Institute, Sonora Cancer Research Center, Mexican Society of Medical Oncology Ciudad Obregon, Sonora, Mexico (Dec 1, 2016)
Rutgers University Seminar Myeloid-derived Suppressor Cells (MDSC): Bad If You Have Cancer; Good If You’re Pregnant Rutgers University Rutgers University (Oct 28, 2016)
Regulatory Myeloid Suppressor Cells Lecture MDSC: Multi-talented immune suppressive cells that mediate both detrimental & beneficial effects Wistar Institute Philadelphia, PA (Jun 16, 2016)
Immunology, Membrane Dynamics, and Beyond: A Symposium in Honor of Professor Michael Edidin Lecture Immune suppression: bad if you have a tumor, but good if you’re pregnant Johns Hopkins University Baltimore, MD (Jun 6, 2016)
Tumor Immunology Meets Oncology (TIMO) Lecture Enhancing antitumor immunity & neutralization of immune suppression in the tumor microenvironment Martin Luther University, Halle-Wittenberg, Germany University Hospital Halle (Apr 29, 2016)
TEDCO Oral Presentation A novel BiTE as an immunotherapy drug for the treatment of cancer TEDCO Columbia, MD (Feb 29, 2016)
IASLC 16th Annual Targeted Therapies of Lung Cancer Conference Lecture Other Immune Suppressive Mechanisms & Their Potential Therapies International Association for the Study of Lung Cancer Santa Monica, CA (Feb 17, 2016)
Joint scientific meeting MedImmune and UMD Lecture A novel recombinant molecule that simultaneously inhibits PDL1/PD1-mediated immune suppression and boosts the activation of tumor-reactive T cells MedImmune/UMD Gaithersberg, MD (Feb 8, 2016)
3rd Annual Summit on Thoracic Malignancies & Head & Neck Cancers Lecture Novel, non-antibody approaches for blocking the PD-1 immune suppressive pathway and enhancing antitumor immunity International Association for the study of lung cancer San Juan, Puerto Rico (Dec 11, 2015)
Seminar Novel approaches for blocking the PD-1 immune suppressive pathway and enhancing antitumor immunity University of Rochester Rochester, NY (Dec 7, 2015)
Lecture Tumor-induced immune suppression: the last obstacle (or just another bump in the road) to global success of cancer immunotherapies? University of Utah Salt Lake City, UT (Aug 19, 2015)
Lecture Myeloid cells as an obstacle to cancer immunotherapy Karolinska Institutet for Cancer Research Stockholm, Sweden (Jun 12, 2015)
Cancer Immunotherapy & Immunomonitoring Conference (CITIM) Lecture how to survive inf you are a myeloid-derived suppressor cell (MDSC) CITIM Society Ljubljana, Slovenia (Apr 27, 2015)
Look Ahead Symposium Keynote/Plenary Address The immune system vs. cancer: winners, losers, and complications UMBC UMBC (Apr 15, 2015)
Seminar Novel approaches for blocking the PD1 immune suppressive pathway and enhancing antitumor immunity Wistar Institute Philadelphia, PA (Apr 13, 2015)
MedImmune Lecture Novel Strategies for Neutralizing PD-1 Pathway-mediated Immune Suppression in Cancer MedImmune, Inc. Gaitherburg, MD (Dec 18, 2014)
Baylor College of Medicine Seminar Inflammation, Alarmins,and Immune Suppression in the Tumor Microenvironment: It’s the RAGE Baylor College of Medicine Dallas, TX (Oct 21, 2014)
UMBC President's Council Oral Presentation Activating a Patient’s Immune System to Destroy Cancer Cells UMBC United States (Jul 20, 2014)
Loyola University Cancer Immunotherapy Retreat Keynote/Plenary Address Inflammation and Immune Suppression in the Tumor Microenvironment Loyola University of Chicago Loyola University, Chicago (Jun 3, 2014)
Univ. of Michigan Immunology Seminar Series Seminar Inflammation, Alarmins,and Immune Suppression in the Tumor Microenvironment: It’s the RAGE Univ. of Michigan, Dept. of Immunology Ann Arbor, MI (Apr 2, 2014)
NIH student and post-doc seminar series Seminar Inflammation-induced immune suppression in cancer: It’s the RAGE NIH NIH, Bethesda, MD (Feb 5, 2014)
Midwinter Immunology conference Lecture Inflammation, Alarmins, and Immune Suppression – It’s the RAGE Midwinter Immunology conference Asilomar, CA (Jan 28, 2014)
Uniformed Services University of the Health Sciences Lecture Inflammation-induced immune suppression in cancer: It’s the RAGE Uniformed Services University of the Health Sciences Bethesda, MD (Nov 22, 2013)
Progress in Vaccination Against Cancer (PIVAC) 15 Lecture The continuing saga of understanding & improving anti-tumor immunity: from cancer vaccines to myeloid-derived suppressor cells & PDL1 Progress in Vaccination Against Cancer Society Tubingen, Germany (Oct 6, 2013)
4th International Symposium on Regulators of Adaptive Immunity Lecture Inflammation-induced immune suppression in cancer: It’s the RAGE Erlangen University U. of Erlangen, Germany (Sep 28, 2013)
Institute for Human Virology Lecture Inflammation-induced immune suppression in cancer: It’s the RAGE Institute for Human Virology Baltimore, MD (Sep 23, 2013)
International Congress of Immunology Lecture Tumor-induced Inflammation and Immune Suppression – It’s the RAGE International Congress of Immunology Milan, Italy (Aug 23, 2013)
Japanese Society of Cancer Immunology Annual meeting Keynote/Plenary Address Inflammation-induced immune suppression in cancer: Myeloid-derived suppressor cells Japanese Society of Cancer Immunology Yamaguchi, Japan (Jul 3, 2013)
The Association for Cancer Immunotherapy (CIMT) annual conference Lecture Inflammation, alarmins, and immune suppression - It's the RAGE CIMT Mainz, Germany (May 1, 2013)
Cancer Immunotherapy and Immunomonitoring (CITIM) Keynote/Plenary Address Inflammation, alarmins, and immune suppression - It's all about RAGE CITIM Krakow, Poland (Apr 22, 2013)
Progress in vaccination against cancer 12 (PIVAC12) Keynote/Plenary Address A tale of two cytokines: inflammation-amplified cross-talk between myeloid cells drives tumor progression. PIVAC Nottingham, UK (Sep 11, 2012)