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Updated: Oct 15, 2025

Preparation of Myeloid Derived Suppressor Cells MDSC from Naive and Pancreatic Tumor-bearing Mice using Flow Cytometry and Automated Magnetic Activated Cell Sorting AutoMACS
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β2-adrenergic receptor signaling regulates metabolic pathways critical to myeloid-derived suppressor cell function

Hemn Mohammadpour1, Cameron R MacDonald1, Philip L McCarthy2

  • 1Department of Immunology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.

Cell Reports
|October 27, 2021
PubMed

Insights

Stress-activated beta-2 adrenergic receptor (β2-AR) signaling in myeloid-derived suppressor cells (MDSCs) drives their immune-suppressive function by altering cell metabolism and increasing prostaglandin E2 (PGE2) release.

Area of Science:

  • Immunology
  • Cancer Biology
  • Metabolic Regulation

Background:

  • Myeloid-derived suppressor cells (MDSCs) are key regulators of the tumor immune microenvironment, suppressing anti-tumor immunity.
  • The precise molecular mechanisms governing MDSC suppressive functions, particularly in response to stress, are not fully understood.
  • Targeting MDSC suppressive mechanisms offers a potential strategy to enhance cancer immunotherapy.

Purpose of the Study:

  • To elucidate the role of the beta-2 adrenergic receptor (β2-AR) stress pathway in regulating MDSC function and metabolism.
  • To identify the metabolic pathways and mediators involved in β2-AR-driven MDSC immunosuppression.

Main Methods:

  • Analysis of β2-AR expression on MDSCs during tumor progression.
  • Metabolic profiling of MDSCs under β2-AR signaling conditions.
  • Assessment of autophagy, fatty acid oxidation (FAO), and prostaglandin E2 (PGE2) production.

Main Results:

  • β2-AR expression on MDSCs increases with tumor growth.
  • β2-AR signaling suppresses glycolysis while enhancing oxidative phosphorylation and FAO, upregulating the transporter CPT1A.
  • β2-AR activation increases autophagy and the arachidonic acid cycle, leading to elevated PGE2 release.

Conclusions:

  • β2-AR signaling, triggered by stress, is a critical regulator of MDSC metabolism and immunosuppressive function.
  • This pathway alters MDSC metabolic reprogramming, promoting FAO and PGE2 production, thereby impeding anti-tumor immunity.
  • Targeting the β2-AR pathway in MDSCs may represent a novel therapeutic approach to augment cancer immunotherapy.
Keywords:
MDSCsautophagycancerfatty acid oxidationimmune suppressionmetabolismoxidative phosphorylationprostaglandin E2stressβ-adrenergic signaling

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