Understanding the role of immature myeloid cells/myeloid-derived suppressor cells in early melanoma establishment 3362

Description Immature myeloid cells (IMC) are continually generated in the bone marrow of healthy individuals where they differentiate into mature myeloid cells (such as neutrophils and monocytes) without causing detectable immunosuppression. In melanoma however, IMC are known to be recruited to the tumor microenvironment and to differentiate into Myeloid-Derived Suppressor Cells (MDSC) with a potent ability to suppress various types of immune responses. We are testing the hypotheses that IMC play a direct role in supporting early melanoma establishment in the first instance by providing growth and angiogenic factors and an indirect role by shielding emerging tumors against early immune attack. Treatment with anti-Gr-1 and anti-Ly6G antibodies depleted subsets of CD11b+ myeloid cells but did not impact the establishment and early growth of B16, YUMM 1.7, or YUMM 3.3 tumors. Furthermore, the co-transfer of CD11b+ myeloid cells from naïve mice alongside reduced numbers of tumor cells into immune-deficient Rag 2 KO mice did not enhance tumor establishment or growth. Together, the data suggest that IMC do not play a direct role in supporting early melanoma growth. However, CD11b+ cells harvested from melanoma-bearing immune-competent mice were found to suppress T cell function in vitro. Next, we will examine the indirect role of IMC in melanoma development by defining the earliest timepoints at which these cells contribute toward the suppression of immune effector cells.