The Role of Protein Kinases in the Suppressive Phenotype of Myeloid-Derived Suppressor Cells

TL;DR

This paper explores how protein kinases influence the immunosuppressive behavior of myeloid-derived suppressor cells during chronic inflammation.

Contribution

The paper highlights recent discoveries on specific protein kinases that directly contribute to the immunosuppressive functions of MDSCs.

Findings

Protein kinases like mTOR, PI3Ks, TAM RTKs, and MAPKs are key regulators of MDSC generation and function.

These kinases play a central role in the signal transduction pathways that drive immunosuppression in MDSCs.

Understanding these mechanisms could lead to new therapeutic strategies for diseases involving chronic inflammation.

Abstract

Inflammation is a self-defense mechanism that controls the homeostasis of an organism, and its alteration by persistent noxious stimuli could lead to an imbalance in the regulation of inflammatory responses mediated by innate and adaptive immunity. During chronic inflammation, sustained exposure of myeloid cells to the various inflammatory signals derived from inflamed tissue could lead to the generation of myeloid cells with an immunosuppressive state, called myeloid-derived suppressor cells (MDSCs), which can exert protective or deleterious functions depending on the nature of signals and the specific inflammatory conditions created by different pathophysiological contexts. Initially identified in various tumor models and cancer patient samples, these cells have long been recognized as negative regulators of anti-tumor immunity. Consequently, researchers have focused on elucidating the molecular mechanisms underlying their potent immunosuppressive activity. As a key component of the signal transducing processes, protein kinases play a central role in regulating the signal transduction mechanisms of many cellular activities, including differentiation and immunosuppression. Over the past decade, at least a dozen kinases, including mechanistic target of rapamycin (mTOR), phosphoinositide 3-kinases (PI3Ks), TAM (Tyro3, Axl, Mer) family of receptor tyrosine kinases (TAM RTKs), mitogen-activated protein kinases (MAPKs), and others, have emerged as key contributors to the generation and differentiation of MDSCs. Here, we discuss the recent findings on these kinases that directly contribute to the immunosuppressive functions of MDSCs.

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