. 2016 Mar; 73(13):2411-24.
doi: 10.1007/s00018-016-2166-5.

Tumor-associated macrophages and anti-tumor therapies: complex links

Cristina Belgiovine 1 Maurizio D'Incalci 2 Paola Allavena 3 Roberta Frapolli 2 
  • PMID: 26956893
  •     172 References
  •     34 citations


Myeloid cells infiltrating the tumor microenvironment, especially tumor-associated macrophages (TAMs), are essential providers of cancer-related inflammation, a condition known to accelerate tumor progression and limit the response to anti-tumor therapies. As a matter of fact, TAMs may have a dual role while interfering with cancer treatments, as they can either promote or impair their functionality. Here we review the connection between macrophages and anticancer therapies; moreover, we provide an overview of the different strategies to target or re-program TAMs for therapeutic purposes.

Keywords: Anti-tumor therapies; Cancer-related inflammation; Macrophage targeting; Nanoparticles; Tumor-associated macrophages.

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The distribution of macrophages with a M1 or M2 phenotype in relation to prognosis and the molecular characteristics of colorectal cancer.
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A review of trabectedin (ET-743): a unique mechanism of action.
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Mol Cancer Ther, 2010 Jul 22; 9(8). PMID: 20647340
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Targeting distinct tumor-infiltrating myeloid cells by inhibiting CSF-1 receptor: combating tumor evasion of antiangiogenic therapy.
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Clodronate-liposome-mediated depletion of tumour-associated macrophages: a new and highly effective antiangiogenic therapy approach.
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Nat Rev Immunol, 2005 Dec 03; 5(12). PMID: 16322748
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Key role for myeloid cells: phase II results of anti-G(D2) antibody 3F8 plus granulocyte-macrophage colony-stimulating factor for chemoresistant osteomedullary neuroblastoma.
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Targeting tumor-associated macrophages with anti-CSF-1R antibody reveals a strategy for cancer therapy.
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Deficiency of the macrophage growth factor CSF-1 disrupts pancreatic neuroendocrine tumor development.
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Eur J Immunol, 2014 May 07; 44(8). PMID: 24796276
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Metastasis in context: modeling the tumor microenvironment with cancer-on-a-chip approaches.
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Interleukin-18 Amplifies Macrophage Polarization and Morphological Alteration, Leading to Excessive Angiogenesis.
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Front Immunol, 2018 Mar 22; 9. PMID: 29559970    Free PMC article.
Repolarizing heterogeneous leukemia-associated macrophages with more M1 characteristics eliminates their pro-leukemic effects.
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Interleukin-1 Beta-A Friend or Foe in Malignancies?
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CD47 Blockade Inhibits Tumor Progression through Promoting Phagocytosis of Tumor Cells by M2 Polarized Macrophages in Endometrial Cancer.
Shenglan Gu, Ting Ni, +7 authors, Yudong Wang.
J Immunol Res, 2018 Dec 14; 2018. PMID: 30525058    Free PMC article.
Programming of macrophages by UV-irradiated apoptotic cancer cells inhibits cancer progression and lung metastasis.
Yong-Bae Kim, Young-Ho Ahn, +3 authors, Jihee Lee Kang.
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Ultrasound Mediated Destruction of LMW-HA-Loaded and Folate-Conjugated Nanobubble for TAM Targeting and Reeducation.
Xiao Sun, Lu Guo, +8 authors, Jie Li.
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Specific Effects of Trabectedin and Lurbinectedin on Human Macrophage Function and Fate-Novel Insights.
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Targeting Tumor-Associated Macrophages in Anti-Cancer Therapies: Convincing the Traitors to Do the Right Thing.
Cristina Belgiovine, Elisabeth Digifico, +2 authors, Fernando Torres Andón.
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Targeting Tumor-Associated Macrophages to Increase the Efficacy of Immune Checkpoint Inhibitors: A Glimpse into Novel Therapeutic Approaches for Metastatic Melanoma.
Claudia Ceci, Maria Grazia Atzori, Pedro Miguel Lacal, Grazia Graziani.
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Zoila Lopez-Bujanda, Charles G Drake.
J Leukoc Biol, 2017 May 28; 102(2). PMID: 28550116    Free PMC article.
Macrophages in Osteosarcoma Immune Microenvironment: Implications for Immunotherapy.
Zhong-Wei Luo, Pan-Pan Liu, +2 authors, Hui Xie.
Front Oncol, 2020 Dec 29; 10. PMID: 33363016    Free PMC article.
The soluble glycoprotein NMB (GPNMB) produced by macrophages induces cancer stemness and metastasis via CD44 and IL-33.
M Liguori, E Digifico, +15 authors, C Belgiovine.
Cell Mol Immunol, 2020 Jul 31; 18(3). PMID: 32728200    Free PMC article.
Targeting macrophages in cancer immunotherapy.
Zhaojun Duan, Yunping Luo.
Signal Transduct Target Ther, 2021 Mar 27; 6(1). PMID: 33767177    Free PMC article.
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Candace C Parker, Suzanne E Lapi.
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High-content and high-throughput identification of macrophage polarization phenotypes.
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Defects in Macrophage Reprogramming in Cancer Therapy: The Negative Impact of PD-L1/PD-1.
Hao Cai, Yichi Zhang, Jian Wang, Jinyang Gu.
Front Immunol, 2021 Jul 13; 12. PMID: 34248982    Free PMC article.
Mesenchymal Stem Cell-Macrophage Crosstalk and Maintenance of Inflammatory Microenvironment Homeostasis.
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Front Cell Dev Biol, 2021 Jul 13; 9. PMID: 34249933    Free PMC article.
Tumor-Associated Macrophages: Combination of Therapies, the Approach to Improve Cancer Treatment.
Pedram Moeini, Paulina Niedźwiedzka-Rystwej.
Int J Mol Sci, 2021 Jul 21; 22(13). PMID: 34281293    Free PMC article.
ERO1L Is a Novel and Potential Biomarker in Lung Adenocarcinoma and Shapes the Immune-Suppressive Tumor Microenvironment.
Lihui Liu, Chao Wang, +6 authors, Jie Wang.
Front Immunol, 2021 Aug 07; 12. PMID: 34354701    Free PMC article.
Macrophages and cancer stem cells: a malevolent alliance.
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Mol Med, 2021 Sep 30; 27(1). PMID: 34583655    Free PMC article.
Macrophage Identification In Situ.
Krisztina Nikovics, Anne-Laure Favier.
Biomedicines, 2021 Oct 24; 9(10). PMID: 34680510    Free PMC article.
Macrophage Polarity and Disease Control.
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Inflammation and Myeloid Cells in Cancer Progression and Metastasis.
Jenying Deng, Jason B Fleming.
Front Cell Dev Biol, 2022 Feb 08; 9. PMID: 35127700    Free PMC article.
Tumor-Associated Macrophages: Reasons to Be Cheerful, Reasons to Be Fearful.
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Exp Suppl, 2022 Feb 16; 113. PMID: 35165862
TLR3 Expression is a Potential Prognosis Biomarker and Shapes the Immune-Active Tumor Microenvironment in Esophageal Squamous Cell Carcinoma.
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J Inflamm Res, 2022 Mar 08; 15. PMID: 35250293    Free PMC article.
Macrophages: shapes and functions.
Uwe Lendeckel, Simone Venz, Carmen Wolke.
ChemTexts, 2022 Mar 16; 8(2). PMID: 35287314    Free PMC article.
Noncoding RNA-mediated macrophage and cancer cell crosstalk in hepatocellular carcinoma.
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