CD14+ hla-DR-/Lo Myeloid-Derived Suppressor Cells Express Immunosuppressive B7-H Family Members and Are Depleted Following Taxane-Based Chemotherapy in Melanoma.

Abstract 464 Myeloid-derived suppressor cells (MDSC) are important, albeit incompletely characterized, immune regulatory cells which suppress host anti-tumor immunity in malignancies like melanoma. We sought to address 3 outstanding questions in the present study: i) does tumor burden drive the expansion of MDSC; ii) do MDSC express immunosuppressive B7-H family members,;iii) are MDSC depleted following chemotherapy administration. As MDSC expand in response to tumor-derived factors, including those elevated in melanoma patients, we hypothesized that the frequency of MDSC present in the peripheral blood of melanoma patients may be dependent on tumor stage. Therefore, PBMC were obtained from both normal donors and melanoma patients with all stages of disease (stage I, n=10; stage II, n=10; stage III, n=10; stage IV, n=47). A discreet population of CD14+HLA-DR-/lo MDSC was appreciated in samples obtained from melanoma patients, but was largely absent in normal donors. Approximately 0.5% of PBMC were CD14+HLA-DR-/lo in normal donors. In contrast, the frequency of these cells progressively increased with tumor stage in melanoma. While a two-fold increase in CD14+HLA-DR-/lo MDSC was observed in stage I patients, this difference did not reach statistical significance. In contrast, a significant increase in CD14+HLA-DR-/lo MDSC was observed in patients with stage II-IV disease (2.2% Stage II, p Disclosures: No relevant conflicts of interest to declare.