Dmitry I. Gabrilovich, MD, PhD
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?
: 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.