Targeting interleukin 4 receptor alpha on tumor-associated macrophages reduces the pro-tumor macrophage phenotype

Amber E. de Groot; Kayla V. Myers; Timothy E.G. Krueger; W. Nathaniel Brennen; Sarah R. Amend; Kenneth J. Pienta

Neoplasia: An International Journal for Oncology Research (Oct 2022)

Targeting interleukin 4 receptor alpha on tumor-associated macrophages reduces the pro-tumor macrophage phenotype

Amber E. de Groot,
Kayla V. Myers,
Timothy E.G. Krueger,
W. Nathaniel Brennen,
Sarah R. Amend,
Kenneth J. Pienta

Affiliations

Amber E. de Groot: Cancer Ecology Center, The Brady Urological Institute, Johns Hopkins School of Medicine, 600 N. Wolfe St., Baltimore, MD, 21287, USA; Department of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, 725 N. Wolfe St., Baltimore, MD, USA
Kayla V. Myers: Cancer Ecology Center, The Brady Urological Institute, Johns Hopkins School of Medicine, 600 N. Wolfe St., Baltimore, MD, 21287, USA; Department of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, 725 N. Wolfe St., Baltimore, MD, USA; Corresponding author.
Timothy E.G. Krueger: Cancer Ecology Center, The Brady Urological Institute, Johns Hopkins School of Medicine, 600 N. Wolfe St., Baltimore, MD, 21287, USA; Department of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, 725 N. Wolfe St., Baltimore, MD, USA; Department of Oncology, Johns Hopkins School of Medicine, 600 N. Wolfe St., Baltimore, MD, 21287, USA
W. Nathaniel Brennen: Cancer Ecology Center, The Brady Urological Institute, Johns Hopkins School of Medicine, 600 N. Wolfe St., Baltimore, MD, 21287, USA; Department of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, 725 N. Wolfe St., Baltimore, MD, USA; Department of Oncology, Johns Hopkins School of Medicine, 600 N. Wolfe St., Baltimore, MD, 21287, USA
Sarah R. Amend: Cancer Ecology Center, The Brady Urological Institute, Johns Hopkins School of Medicine, 600 N. Wolfe St., Baltimore, MD, 21287, USA; Department of Oncology, Johns Hopkins School of Medicine, 600 N. Wolfe St., Baltimore, MD, 21287, USA
Kenneth J. Pienta: Cancer Ecology Center, The Brady Urological Institute, Johns Hopkins School of Medicine, 600 N. Wolfe St., Baltimore, MD, 21287, USA; Department of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, 725 N. Wolfe St., Baltimore, MD, USA; Department of Oncology, Johns Hopkins School of Medicine, 600 N. Wolfe St., Baltimore, MD, 21287, USA; Department of Chemical and Biomolecular Engineering, Johns Hopkins Whiting School of Engineering, 3400 N. Charles St., Baltimore, MD, 21218, USA

Journal volume & issue: Vol. 32
p. 100830

Abstract

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Tumor-associated macrophages (TAMs) are an abundant tumor-promoting cell type in the tumor microenvironment (TME). Most TAMs exhibit a pro-tumor M2-like phenotype supportive of tumor growth, immune evasion, and metastasis. IL-4 and IL-13 are major cytokines that polarize macrophages to an M2 subset and share a common receptor, IL-4 receptor alpha (IL-4R alpha). Treatment of human ex vivo polarized M2 macrophages and M2 macrophage precursors with IL-4R alpha antagonist antibody Dupilumab (DupixentⓇ) reduces M2 macrophage features, including a shift in cell surface marker protein expression and gene expression. In animal models of prostate cancer, both pharmacologic inhibition of IL-4R alpha and genetic deletion of IL-4R alpha utilizing an Il4ra -/- mouse model result in decreased CD206 on TAMs. These data support IL-4R alpha as a target to reduce the pro-tumor, M2-like macrophage phenotype as a novel adjunct cancer therapy.

Published in Neoplasia: An International Journal for Oncology Research

ISSN: 1522-8002 (Print); 1476-5586 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: http://www.journals.elsevier.com/neoplasia/

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Abstract

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