Myeloid derived suppressor cells (MDSCs) are a subset of myeloid precursors that are only present in pathological situations such as pathogen infection and cancer. Very little is known about the regulation of this cells as well as the regulation of its immunosuppressive function. We are interested in whether MDSC abundance is regulated by tumor cells secreted factors as a means to evade anti-tumor immune responses and how this might be affected by radiation therapy. Our hypothesis is that radiation therapy activation of TGFβ, which has a prominent role in the induction and maintenance of MDSC, promotes MDSC in the tumor microenvironment, thereby limiting tumor control. To test this we first established co-cultures of tumor cell lines and freshly isolated PBMCs from normal donors. MDSC are rarely in healthy donor mono-cultures (less than 1%). However, co-culture with either MDA-MB231 breast cancer cell line or with U118-MG glioma cancer cells resulted in a significant enrichment in the population of MDSCs (up to 12%). We then isolated cells based on CD33 expression for functional characterization. Compared to CD33- cells, the CD33+ population expresses significantly higher levels of ARG1, PDL1, IL10 and TGFB1, which are markers of active MDSC. This model will be modified by co-culture with irradiated tumor cell lines in conjunction with TGFβ inhibitors in ongoing studies. We can postulate that the combination of radiotherapy and TGFβ inhibitors, which are nowadays in clinical trials for different cancer types, could have important therapeutic benefits.
Citation Format: Alba Gonzalez-Junca, Ilenia Pelicciotta, Kyla Elizabeth Discroll, Mary Helen Barcellos-Hoff. The role of radiation-induced TGF-β in the generation of MDSCs. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy: A New Chapter; December 1-4, 2014; Orlando, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2015;3(10 Suppl):Abstract nr A17.
- ©2015 American Association for Cancer Research.