Targeting interleukin 4 receptor alpha on tumor-associated macrophages reduces the pro-tumor macrophage phenotype
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...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-10-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558622000574 |
| _version_ | 1817999349943107584 |
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| author | Amber E. de Groot Kayla V. Myers Timothy E.G. Krueger W. Nathaniel Brennen Sarah R. Amend Kenneth J. Pienta |
| author_facet | Amber E. de Groot Kayla V. Myers Timothy E.G. Krueger W. Nathaniel Brennen Sarah R. Amend Kenneth J. Pienta |
| author_sort | Amber E. de Groot |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-14T03:07:28Z |
| format | Article |
| id | doaj.art-cb19fe109d0b4254af26572f404fa1e7 |
| institution | Directory Open Access Journal |
| issn | 1476-5586 |
| language | English |
| last_indexed | 2024-04-14T03:07:28Z |
| publishDate | 2022-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-cb19fe109d0b4254af26572f404fa1e72022-12-22T02:15:41ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55862022-10-0132100830Targeting interleukin 4 receptor alpha on tumor-associated macrophages reduces the pro-tumor macrophage phenotypeAmber E. de Groot0Kayla V. Myers1Timothy E.G. Krueger2W. Nathaniel Brennen3Sarah R. Amend4Kenneth J. Pienta5Cancer 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, USACancer 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.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, USACancer 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, USACancer 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, USACancer 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, USATumor-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.http://www.sciencedirect.com/science/article/pii/S1476558622000574Prostate cancerMacrophageIL-4R alphaIL-4DupilumabDupixent |
| spellingShingle | Amber E. de Groot Kayla V. Myers Timothy E.G. Krueger W. Nathaniel Brennen Sarah R. Amend Kenneth J. Pienta Targeting interleukin 4 receptor alpha on tumor-associated macrophages reduces the pro-tumor macrophage phenotype Neoplasia: An International Journal for Oncology Research Prostate cancer Macrophage IL-4R alpha IL-4 Dupilumab Dupixent |
| title | Targeting interleukin 4 receptor alpha on tumor-associated macrophages reduces the pro-tumor macrophage phenotype |
| title_full | Targeting interleukin 4 receptor alpha on tumor-associated macrophages reduces the pro-tumor macrophage phenotype |
| title_fullStr | Targeting interleukin 4 receptor alpha on tumor-associated macrophages reduces the pro-tumor macrophage phenotype |
| title_full_unstemmed | Targeting interleukin 4 receptor alpha on tumor-associated macrophages reduces the pro-tumor macrophage phenotype |
| title_short | Targeting interleukin 4 receptor alpha on tumor-associated macrophages reduces the pro-tumor macrophage phenotype |
| title_sort | targeting interleukin 4 receptor alpha on tumor associated macrophages reduces the pro tumor macrophage phenotype |
| topic | Prostate cancer Macrophage IL-4R alpha IL-4 Dupilumab Dupixent |
| url | http://www.sciencedirect.com/science/article/pii/S1476558622000574 |
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