Effect of chemotherapy on the myeloid-derived suppressor cells percentages in the peripheral blood of advanced non-small cell lung cancer patients (TUM6P.965)

Abstract

Abstract In our previous study, high levels of one granulocytic (G-MDSC) and two monocytic (M-MDSCs) subpopulations of immunosuppressive MDSCs were found and their overexpression was correlated with worse prognosis in NSCLC patients. Using flow cytometry, the impact of chemotherapy on the percentages and functionality of M-MDSC (CD14+CD15-CD11b+CD33+HLA-DR-Lin- and CD14+CD15+CD11b+ CD33+HLA-DR-Lin-) and G-MDSC (CD14-CD15+CD11b+CD33+HLA-DR-Lin-) was evaluated in the peripheral blood of patients (n=141) prior to chemotherapy and after the 3rd and 6th cycle of treatment. The M-MDSC (CD14+CD15-CD11b+CD33+HLA-DR-Lin-) percentages were found significantly decreased post chemotherapy compared to baseline, whereas chemotherapy had no effect on CD14+CD15+CD11b+CD33+HLA-DR-Lin- M-MDSCs. In contrast, the production of iNOS by M-MDSCs was significantly increased compared to the baseline. Both G-MDSC levels and their ROS expression were not affected by chemotherapy. In addition, both subtypes of MDSCs, when co-cultured with CD3+ T cells, were able to significantly suppress IFN-γ secretion by T cells. Finally, the M-MDSC (CD14+CD15-CD11b+CD33+HLA-DR-Lin-) percentages were found significantly decreased in patients that did not develop progressive disease during or after treatment completion, compared to patients with disease progression. Chemotherapy seems to have an impact on MDSC expression and functionality, hence targeting these cells may lead to a better clinical outcome in NSCLC patients.