Since the early 2000’s they have been identifying and studying immune suppressive components in the tumor microenvironment.  Her lab was among the first labs to appreciate that myeloid-derived suppressor cells (MDSC) are highly immune suppressive cells present in virtually all cancer patients. figure1.png MDSC are a significant obstacle to active cancer immunotherapies because they promote tumor growth through a variety of immune and non-immune mechanisms including inhibiting the activation and function of T cells and polarizing macrophages towards a tumor-promoting phenotype. Their work demonstrating that MDSC are induced by a variety of pro-inflammatory mediators is the basis for the concept that chronic inflammation increases cancer risk and cancer progression by inducing MDSC. Her lab was also the first to demonstrate that macrophages, another major pro-tumor myeloid cell population that infiltrates solid tumors, undergo crosstalk with MDSC, which enhances the pro-tumor activity of both cell populations.  The lab’s studies have identified a variety of physiological conditions and molecules that drive the accumulation and suppressive potency of MDSCs.  In collaboration with the lab of Dr. Catherine Fenselau (Univ. Maryland College Park) using mass spectrometry and proteomic techniques, the lab has shown that tumor-induced MDSC produce exosomes that contain proteins, mRNAs and microRNAs that regulate MDSC functions including macrophage polarization and MDSC chemotaxis and migration.

figure2.pngBecause of the increasing health risks associated with obesity, her lab recently investigated the linkage between MDSC, obesity, high fat diet, and cancer. These studies have demonstrated that obesity enhances the accumulation of MDSC and that the MDSC, in turn, contribute to the more rapid growth of tumors in obese individuals.  Although high fat diet-driven MDSCs contribute to tumor progression, they protect against some of the metabolic dysfunction associated with high fat diet and therefore have both detrimental and beneficial functions.

figure3.pngHer lab has also demonstrated that in contrast to cancer, MDSC have a beneficial role during pregnancy where they prevent the mother’s T cells from rejecting an allogeneic fetus.  The lab has also explored novel strategies that combine the activation of tumor-reactive T cells and simultaneously blocking the programmed death 1 (PD-1) pathway (checkpoint blockade).  One of these immunotherapies uses a soluble form of the costimulatory molecule CD80 to activate T cells through CD28 while concurrently binding to PD-L1, the ligand for PD-1.  A second approach uses a bispecific T cell engager (CD3xPDL1 BiTE) that activates T cells through CD3 and prevents PD-1/PD-L1 interactions by binding to PD-L1. 

Dr. Ostrand-Rosenberg is co-Editor-in-Chief of the journal Cancer Immunology, Immunotherapy.

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Sue Ostrand-Rosenberg, PhD

Adjunct Professor of Pathology
Member, Huntsman Cancer Institute
University of Utah

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