Date on Master's Thesis/Doctoral Dissertation
Microbiology and Immunology
Microbiology and Immunology, PhD
glucan; tumor; cancer; immunity; myeloid; suppressor
Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of immature myeloid cells that promote tumor progression. In this study, we investigated the effect of dectin-1 stimulation by yeast-derived particulate β-glucan in MDSC function and differentiation in cancer. In vivo treatment of mice bearing lewis lung carcinoma and mammary cell carcinoma with particulate β-glucan decreased tumor weight and splenomegaly, and reduced the accumulation of polymorphonuclear-MDSC (PMN-MDSC) but not monocytic-MDSC (M-MDSC) in the spleen and tumor. In addition, particulate β-glucan differentially modulated the function of different MDSC subsets; it enhanced PMN-MDSC respiratory burst and apoptosis, and induced the differentiation of M-MDSC into F4/80+CD11c+antigen-presenting cells in a dectin-1 dependent manner. ERK1/2 phosphorylation was also required for the acquisition of APC properties in M-MDSC. Moreover, M-MSDC treated with particulate β-glucan did not promote tumor growth in vivo when inoculated with LLC subcutaneously. To evaluate the effect of particulate β-glucan treatment in humans, patients with non-small cell lung cancer (NSCL) were treated with particulate β-glucan for two weeks prior to any other treatment and surgical excision of the tumor. Strikingly, the frequency of CD14-HLA-DR-CD11b+CD33+ MDSC decreased in the peripheral blood, and arginase-1 expression significantly decreased in a cohort of 15 patients. This study was the first to assess the effect of particulate β-glucan on MDSC in lung cancer patients, towards a future inclusion of particulate β-glucan in combination therapies in lung cancer.
Albeituni, Sabrin Husein, "Immunomodulation of myeloid-derived suppressor cells by particulate b-glucan in cancer." (2015). Electronic Theses and Dissertations. Paper 2332.