[Frontiers in Bioscience E4, 1237-1245, January 1, 2012]

Natural suppressor cells; past, present and future

Parvin Forghani1, M.R. Khorramizadeh1, Edmund K. Waller2

1School of Public Health, Dept of Medical Biotechnology, School of Advanced Medical Technologies Tehran University of Medical Sciences, Tehran, Iran, 2Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA

TABLE OF CONTENTS

1. Abstract
2. History of Natural Suppressor Cells
3. Features of MDSCs
3.1. Cell surface molecules & nuclear morphology definitions
3.2. Suppressive properties
3.3. Molecular Mechanisms of suppressor activity of MDSCs
3.3.1. No - dependent mechanisms
3.3.1.1. iNOS & Arginase (ARG1) up regulation
3.3.1.2. ROS-mediated cell killing
3.3.2. No-independent mechanisms
3.3.2.1. Blocking of NK cytotoxicity
3.3.2.2. Development of Foxp3+ T regs
3.3.2.3. Skewing of macrophage/ neutrophil activity
3.3.2.4. Down regulation of L-selectin
3.3.2.5. Cystine Sequestration
3.4. Activation & expansion o f MDSCs
3.4.1. Cytokine-dependence of MDSC
3.4.2 ..Modulation of VEGF signaling by MDSC
3.4.3. Tumor-directed myeloid differentiation towards MDSC
3.5. Perspective
4. Summary
5. References

1. ABSTRACT

Myeloid Derived Suppressor Cells (MDSCs) are a mixed group of bone marrow-derived myeloid cells containing macrophages, granulocytes, immature DCs and early myeloid precursors that have immune suppressive activity (1). MDSCs infiltrate the BM, spleen and peripheral blood of tumors-bearing experimental animals and are found in the blood of cancer patients as a result of tumor-induced alterations in myelopoiesis. Evidence from murine model systems indicated that myeloid-derived cells with suppressor activity also accumulate in non-tumor bearing hosts in response to infection, chemotherapy (2), stress (3), and immune senescence(4). MDSCs are considered key negative regulators of immune responses. Their association with tumor-associated immune defects make MDSCs an