Meme Kanseri Modelinde Myeloid Kökenli Hücrelerin Immün Kompartmanlardaki Dağılımının Anti-Tümör Yanıtlara Yansıması

Abstract

Myeloid cells of peripheral blood, bone marrow and spleens from NMU induced mammary tumor bearing Sprague-Dawley rats were examined in this study. Myeloid derived suppressor cells (MDSCs) in tumor bearing rats are defined with CD11b/c+ HIS48+ immunophenotype. As this definition addresses both granulocytic and monocytic populations, we separated neutrophils from monocytic populations according to Rp-1 expression and classified monocytes into two sub groups regarding the HIS48 positivity. The RP-1+ neutrophil amounts increased prominently in peripheral blood and spleens of mammary tumor bearing Sprague Dawley rats. Rp-1+ neutrophils also suppressed the antigen specific CD4+ T cell proliferations. These neutrophils were the dominant suppressor populations and corresponded to the granulocytic-MDSCs. Reactive oxygen species (ROS), nitric oxide (NO) productions and TGF-β synthesis were found to be responsible for the suppressive effect of these neutrophils. Additionally, HIS48+ monocytes of tumor hosts had lower MHC class II expression, higher nitric oxide and TGF-β productions than HIS48- monocytes resembling the monocytic-MDSCs of mice. Here we report Rp-1 antibody as a specific marker to distinguish rat PMNMDSCs. Additionally, we identified two functionally different monocyte subsets based on HIS48 staining. Granulocytic subset of tumor bearing rat MDSCs were defined as Rp-1+ HIS48+ neutrophils. Two functionally and morphologically different subsets of RP-1- rat monocytes were discriminated by HIS48 staining.