Suzanne Ostrand-rosenberg

Biography

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 Interest

Tumor/cancer immunology; tumor-induced immune suppression; cancer vaccine development