In 2007 the Food and Drug Administration revised the guidelines for the administration of erythropoietin (EPO), a recombinant biologic drug used to treat the anemia generated following chemotherapy and radiation treatment in cancer patients. EPO had been found to accelerate disease progression and increase mortality in patients with several forms of cancer. As investigators sought an explanation for this observation conflicting data emerged regarding the presence of EPO receptors on tumor cells. We propose that EPO receptor expression by tumor cells is not solely required for cancer progression. Instead we propose that EPO could act directly upon cells of the immune system, in the tumor microenvironment, to increase macrophage-mediated immune suppression. Our preliminary results show that EPO has no effect upon T cell activation at macrophage - T cell ratios found in normal lymphoid tissues but can enhance suppression as macrophage - T cell interaction is increased, i.e., conditions characteristic of the tumor microenvironment. We will determine the mechanism of EPO-mediated suppression in an in vitro model of the tumor microenvironment. We will also study the effect of EPO administration in a mouse ovarian cancer model to examine how EPO suppresses anti-tumor immunity in vivo. Results from these studies will be relevant not only to strategies used to treat anemia but also those designed to reverse the immune suppression characteristic of cancer.
Conventional chemotherapy and radiation treatment often lead to anemia in cancer patients. Erythropoietin (EPO), a biologic drug commonly used to treat anemia, has been found to accelerate the progression of cancer in these patients. Although research has focused on how this molecule impacts cancer cells, an alternative hypothesis is that the immune system needed to control the cancer is being suppressed by EPO. Further understanding how EPO influences immunity could foster the development of novel strategies for therapeutic intervention for anemia and cancer treatment.
| Goldman, Naomi; Lomakova, Yelizavet D; Londregan, Jennifer et al. (2018) High macrophage PD-L1 expression not responsible for T cell suppression. Cell Immunol 324:50-58 |
| Goldman, Naomi; Valiuskyte, Kornelija; Londregan, Jennifer et al. (2017) Macrophage regulation of B cell proliferation. Cell Immunol 314:54-62 |
| Wood, Michelle A; Goldman, Naomi; DePierri, Kelley et al. (2016) Erythropoietin increases macrophage-mediated T cell suppression. Cell Immunol 306-307:17-24 |
