Peptide-based systems analysis of inflammation induced myeloid-derived suppressor cells reveals diverse signaling pathways

基于肽的系统分析炎症诱导的髓系抑制细胞揭示了多种信号通路

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作者:Waeowalee Choksawangkarn, Lauren M Graham, Meghan Burke, Sang Bok Lee, Suzanne Ostrand-Rosenberg, Catherine Fenselau, Nathan J Edwards

Abstract

A better understanding of molecular signaling between myeloid-derived suppressor cells (MDSC), tumor cells, T-cells, and inflammatory mediators is expected to contribute to more effective cancer immunotherapies. We focus on plasma membrane associated proteins, which are critical in signaling and intercellular communication, and investigate changes in their abundance in MDSC of tumor-bearing mice subject to heightened versus basal inflammatory conditions. Using spectral counting, we observed statistically significant differential abundances for 35 proteins associated with the plasma membrane, most notably the pro-inflammatory proteins S100A8 and S100A9 which induce MDSC and promote their migration. We also tested whether the peptides associated with canonical pathways showed a statistically significant increase or decrease subject to heightened versus basal inflammatory conditions. Collectively, these studies used bottom-up proteomic analysis to identify plasma membrane associated pro-inflammatory molecules and pathways that drive MDSC accumulation, migration, and suppressive potency.

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