Date on Master's Thesis/Doctoral Dissertation
12-2015
Document Type
Doctoral Dissertation
Degree Name
Ph. D.
Department
Microbiology and Immunology
Degree Program
Microbiology and Immunology, PhD
Committee Chair
Yan, Jun
Committee Member
Shirwan, Haval
Committee Member
Zhang, Huang-ge
Committee Member
Suttles, Jill
Committee Member
Uriarte, Silvia
Author's Keywords
glucan; tumor; cancer; immunity; myeloid; suppressor
Abstract
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.
Recommended Citation
Albeituni, Sabrin Husein, "Immunomodulation of myeloid-derived suppressor cells by particulate b-glucan in cancer." (2015). Electronic Theses and Dissertations. Paper 2332.
https://doi.org/10.18297/etd/2332
