. 2021 Sep; 10(9):.
doi: 10.3390/cells10092364.

Bringing Macrophages to the Frontline against Cancer: Current Immunotherapies Targeting Macrophages

Mariana Reis-Sobreiro 1 Afonso Teixeira da Mota 1 Carolina Jardim 1 Karine Serre 1 
  • PMID: 34572013
  •     322 References


Macrophages are found in all tissues and display outstanding functional diversity. From embryo to birth and throughout adult life, they play critical roles in development, homeostasis, tissue repair, immunity, and, importantly, in the control of cancer growth. In this review, we will briefly detail the multi-functional, protumoral, and antitumoral roles of macrophages in the tumor microenvironment. Our objective is to focus on the ever-growing therapeutic opportunities, with promising preclinical and clinical results developed in recent years, to modulate the contribution of macrophages in oncologic diseases. While the majority of cancer immunotherapies target T cells, we believe that macrophages have a promising therapeutic potential as tumoricidal effectors and in mobilizing their surroundings towards antitumor immunity to efficiently limit cancer progression.

Keywords: antitumor functions; macrophages; myeloid-targeted therapies; reprogramming.

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J Hematol Oncol, 2020 Nov 13; 13(1). PMID: 33176869    Free PMC article.
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Cancer Res, 2002 Sep 05; 62(17). PMID: 12208763
RIG-I Promotes Cell Death in Hepatocellular Carcinoma by Inducing M1 Polarization of Perineal Macrophages Through the RIG-I/MAVS/NF-κB Pathway.
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Immune Cell PD-L1 Colocalizes with Macrophages and Is Associated with Outcome in PD-1 Pathway Blockade Therapy.
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Chih-Chan Lee, Jiunn-Chang Lin, +5 authors, Muh-Hwa Yang.
Nat Commun, 2018 Sep 16; 9(1). PMID: 30218063    Free PMC article.
Tumor Killing by CD4+ T Cells Is Mediated via Induction of Inducible Nitric Oxide Synthase-Dependent Macrophage Cytotoxicity.
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Front Immunol, 2018 Aug 08; 9. PMID: 30083157    Free PMC article.
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Delivery of 5'-triphosphate RNA with endosomolytic nanoparticles potently activates RIG-I to improve cancer immunotherapy.
Max E Jacobson, Lihong Wang-Bishop, Kyle W Becker, John T Wilson.
Biomater Sci, 2018 Nov 01; 7(2). PMID: 30379158
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Anticancer Res, 2005 Apr 09; 25(1B). PMID: 15816613
Mammary Tumor Cells with High Metastatic Potential Are Hypersensitive to Macrophage-Derived HGF.
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Nat Immunol, 2012 Oct 02; 13(11). PMID: 23023392    Free PMC article.
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Nat Med, 2013 Sep 24; 19(10). PMID: 24056773    Free PMC article.
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An interferon-γ-delivery system based on chitosan/poly(γ-glutamic acid) polyelectrolyte complexes modulates macrophage-derived stimulation of cancer cell invasion in vitro.
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Acta Biomater, 2015 May 28; 23. PMID: 26013040
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Cell Metab, 2019 Apr 02; 29(6). PMID: 30930171
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Phase 2 study of carlumab (CNTO 888), a human monoclonal antibody against CC-chemokine ligand 2 (CCL2), in metastatic castration-resistant prostate cancer.
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BTN3A2 expression in epithelial ovarian cancer is associated with higher tumor infiltrating T cells and a better prognosis.
Cécile Le Page, Alexandre Marineau, +8 authors, Jean-François Cailhier.
PLoS One, 2012 Jun 12; 7(6). PMID: 22685580    Free PMC article.
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Blockade of the Phagocytic Receptor MerTK on Tumor-Associated Macrophages Enhances P2X7R-Dependent STING Activation by Tumor-Derived cGAMP.
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Immunity, 2020 Feb 13; 52(2). PMID: 32049051
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Nature, 2016 Nov 01; 539(7629). PMID: 27642729    Free PMC article.
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Cancer Immunol Immunother, 2017 Feb 12; 66(4). PMID: 28184968    Free PMC article.
Real-Time Imaging Reveals Local, Transient Vascular Permeability, and Tumor Cell Intravasation Stimulated by TIE2hi Macrophage-Derived VEGFA.
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Cancer Discov, 2015 Aug 14; 5(9). PMID: 26269515    Free PMC article.
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Antonio Macciò, Giulia Gramignano, +3 authors, Clelia Madeddu.
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Primary Tumors Limit Metastasis Formation through Induction of IL15-Mediated Cross-Talk between Patrolling Monocytes and NK Cells.
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Cancer Immunol Res, 2017 Aug 16; 5(9). PMID: 28811289
Imaging the mechanisms of anti-CD20 therapy in vivo uncovers spatiotemporal bottlenecks in antibody-dependent phagocytosis.
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Sumiya Ishigami, Shoji Natsugoe, +6 authors, Takashi Aikou.
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Pharmacological inactivation of the PI3K p110δ prevents breast tumour progression by targeting cancer cells and macrophages.
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Cell Death Dis, 2018 Jun 09; 9(6). PMID: 29880805    Free PMC article.
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Arginase inhibition suppresses lung metastasis in the 4T1 breast cancer model independently of the immunomodulatory and anti-metastatic effects of VEGFR-2 blockade.
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A Network of Macrophages Supports Mitochondrial Homeostasis in the Heart.
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Cell, 2020 Sep 17; 183(1). PMID: 32937105
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J Immunother Cancer, 2020 Oct 30; 8(2). PMID: 33115946    Free PMC article.
Prognostic Value of Macrophage Phenotypes in Resectable Non-Small Cell Lung Cancer Assessed by Multiplex Immunohistochemistry.
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J Immunother Cancer, 2020 Oct 25; 8(2). PMID: 33097612    Free PMC article.
Macrophage Blockade Using CSF1R Inhibitors Reverses the Vascular Leakage Underlying Malignant Ascites in Late-Stage Epithelial Ovarian Cancer.
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Antagonistic Inflammatory Phenotypes Dictate Tumor Fate and Response to Immune Checkpoint Blockade.
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TGF-β secreted by tumor-associated macrophages promotes proliferation and invasion of colorectal cancer via miR-34a-VEGF axis.
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Tumor-associated macrophages are associated with response to neoadjuvant chemotherapy and poor outcomes in patients with triple-negative breast cancer.
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Cancer Chemother Pharmacol, 2013 Feb 07; 71(4). PMID: 23385782
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Carlumab, an anti-C-C chemokine ligand 2 monoclonal antibody, in combination with four chemotherapy regimens for the treatment of patients with solid tumors: an open-label, multicenter phase 1b study.
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Cancer Immunol Res, 2018 Jul 18; 6(10). PMID: 30012633
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CXCL9-expressing tumor-associated macrophages: new players in the fight against cancer.
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Significance of macrophage chemoattractant protein-1 in macrophage recruitment, angiogenesis, and survival in human breast cancer.
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PD-1 siRNA-Encapsulated Solid Lipid Nanoparticles Downregulate PD-1 Expression by Macrophages and Inhibit Tumor Growth : PD-1 siRNA-Encapsulated Solid Lipid Nanoparticles.
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Liposomal CpG-ODN: An in vitro and in vivo study on macrophage subtypes responses, biodistribution and subsequent therapeutic efficacy in mice models of cancers.
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Boosting anti-PD-1 therapy with metformin-loaded macrophage-derived microparticles.
Zhaohan Wei, Xiaoqiong Zhang, +13 authors, Xiangliang Yang.
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Cell, 2014 Dec 07; 159(6). PMID: 25480296    Free PMC article.
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Nanoparticle Delivery of RIG-I Agonist Enables Effective and Safe Adjuvant Therapy in Pancreatic Cancer.
Manisit Das, Limei Shen, +2 authors, Leaf Huang.
Mol Ther, 2018 Dec 14; 27(3). PMID: 30545600    Free PMC article.
A CD40 Agonist and PD-1 Antagonist Antibody Reprogram the Microenvironment of Nonimmunogenic Tumors to Allow T-cell-Mediated Anticancer Activity.
Hayley S Ma, Bibhav Poudel, +9 authors, Elizabeth M Jaffee.
Cancer Immunol Res, 2019 Jan 16; 7(3). PMID: 30642833    Free PMC article.
Coupled scRNA-Seq and Intracellular Protein Activity Reveal an Immunosuppressive Role of TREM2 in Cancer.
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Cell, 2020 Aug 14; 182(4). PMID: 32783915
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Murine CD27(-) Vγ6(+) γδ T cells producing IL-17A promote ovarian cancer growth via mobilization of protumor small peritoneal macrophages.
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Tumor-Targeted Drug and CpG Delivery System for Phototherapy and Docetaxel-Enhanced Immunotherapy with Polarization toward M1-Type Macrophages on Triple Negative Breast Cancers.
Lv Chen, Lulu Zhou, +9 authors, Chunyan Dong.
Adv Mater, 2019 Nov 14; 31(52). PMID: 31721331
Increased Antiangiogenic Effect by Blocking CCL2-dependent Macrophages in a Rodent Glioblastoma Model: Correlation Study with Dynamic Susceptibility Contrast Perfusion MRI.
Hye Rim Cho, Nisha Kumari, +3 authors, Seung Hong Choi.
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Cancer Cell, 2005 Oct 18; 8(4). PMID: 16226705
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Therapeutic targeting of macrophages enhances chemotherapy efficacy by unleashing type I interferon response.
Camilla Salvagno, Metamia Ciampricotti, +15 authors, Karin E de Visser.
Nat Cell Biol, 2019 Mar 20; 21(4). PMID: 30886344    Free PMC article.
The degree of macrophage infiltration into the cancer cell nest is a significant predictor of survival in gastric cancer patients.
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COX-2 inhibition alters the phenotype of tumor-associated macrophages from M2 to M1 in ApcMin/+ mouse polyps.
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Lysophospholipids secreted by splenic macrophages induce chemotherapy resistance via interference with the DNA damage response.
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Nat Commun, 2014 Nov 13; 5. PMID: 25387467
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TRAIL-induced programmed necrosis as a novel approach to eliminate tumor cells.
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Metastasis-associated macrophages constrain antitumor capability of natural killer cells in the metastatic site at least partially by membrane bound transforming growth factor β.
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CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis.
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Class IIa HDAC inhibition reduces breast tumours and metastases through anti-tumour macrophages.
Jennifer L Guerriero, Alaba Sotayo, +11 authors, Anthony Letai.
Nature, 2017 Mar 09; 543(7645). PMID: 28273064    Free PMC article.
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EGFR has a tumour-promoting role in liver macrophages during hepatocellular carcinoma formation.
Hanane Lanaya, Anuradha Natarajan, +11 authors, Maria Sibilia.
Nat Cell Biol, 2014 Sep 01; 16(10). PMID: 25173978    Free PMC article.
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C Wyatt Shields, Michael A Evans, +8 authors, Samir Mitragotri.
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The chemokine RANTES is secreted by human melanoma cells and is associated with enhanced tumour formation in nude mice.
U Mrowietz, U Schwenk, +5 authors, D Schadendorf.
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Sunitinib inhibition of Stat3 induces renal cell carcinoma tumor cell apoptosis and reduces immunosuppressive cells.
Hong Xin, Chunyan Zhang, +3 authors, Hua Yu.
Cancer Res, 2009 Feb 27; 69(6). PMID: 19244102    Free PMC article.
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Macrophages Facilitate Resistance to Anti-VEGF Therapy by Altered VEGFR Expression.
Heather J Dalton, Sunila Pradeep, +22 authors, Anil K Sood.
Clin Cancer Res, 2017 Sep 01; 23(22). PMID: 28855350    Free PMC article.
Macrophage-secreted granulin supports pancreatic cancer metastasis by inducing liver fibrosis.
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Nat Cell Biol, 2016 Apr 19; 18(5). PMID: 27088855    Free PMC article.
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Effect of recombinant human tumor necrosis factor on the induction of murine macrophage tumoricidal activity.
K Hori, M J Ehrke, +4 authors, E Mihich.
Cancer Res, 1987 Jun 01; 47(11). PMID: 2882835
Rapid activation of tumor-associated macrophages boosts preexisting tumor immunity.
Sabine Hoves, Chia-Huey Ooi, +15 authors, Carola H Ries.
J Exp Med, 2018 Feb 14; 215(3). PMID: 29436396    Free PMC article.
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TLR7 and TLR9 ligands regulate antigen presentation by macrophages.
Teja Celhar, Selma Pereira-Lopes, +7 authors, Anna-Marie Fairhurst.
Int Immunol, 2015 Nov 15; 28(5). PMID: 26567289    Free PMC article.
M-1/M-2 macrophages and the Th1/Th2 paradigm.
C D Mills, K Kincaid, +2 authors, A M Hill.
J Immunol, 2000 Jun 08; 164(12). PMID: 10843666
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Total absence of colony-stimulating factor 1 in the macrophage-deficient osteopetrotic (op/op) mouse.
W Wiktor-Jedrzejczak, A Bartocci, +4 authors, E R Stanley.
Proc Natl Acad Sci U S A, 1990 Jun 01; 87(12). PMID: 2191302    Free PMC article.
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Cyclooxygenase-2 in tumor-associated macrophages promotes breast cancer cell survival by triggering a positive-feedback loop between macrophages and cancer cells.
Hongzhong Li, Bing Yang, +6 authors, Guosheng Ren.
Oncotarget, 2015 Sep 12; 6(30). PMID: 26359357    Free PMC article.
6-Gingerol as an arginase inhibitor prevents urethane-induced lung carcinogenesis by reprogramming tumor supporting M2 macrophages to M1 phenotype.
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Food Funct, 2018 Aug 29; 9(9). PMID: 30151521
Phosphatidylserine-dependent ingestion of apoptotic cells promotes TGF-beta1 secretion and the resolution of inflammation.
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J Clin Invest, 2002 Jan 10; 109(1). PMID: 11781349    Free PMC article.
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COX2/mPGES1/PGE2 pathway regulates PD-L1 expression in tumor-associated macrophages and myeloid-derived suppressor cells.
Victor Prima, Lyudmila N Kaliberova, +2 authors, Sergei Kusmartsev.
Proc Natl Acad Sci U S A, 2017 Jan 18; 114(5). PMID: 28096371    Free PMC article.
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Targeting MARCO and IL37R on Immunosuppressive Macrophages in Lung Cancer Blocks Regulatory T Cells and Supports Cytotoxic Lymphocyte Function.
Linnéa La Fleur, Johan Botling, +9 authors, Dhifaf Sarhan.
Cancer Res, 2020 Dec 10; 81(4). PMID: 33293426
Toll-Like Receptor Ligands and Interferon-γ Synergize for Induction of Antitumor M1 Macrophages.
Elisabeth Müller, Panagiotis F Christopoulos, +5 authors, Alexandre Corthay.
Front Immunol, 2017 Nov 11; 8. PMID: 29123526    Free PMC article.
Tumoral Immune Cell Exploitation in Colorectal Cancer Metastases Can Be Targeted Effectively by Anti-CCR5 Therapy in Cancer Patients.
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Cancer Cell, 2016 Apr 14; 29(4). PMID: 27070705
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Targeting myeloid-derived suppressor cells with colony stimulating factor-1 receptor blockade can reverse immune resistance to immunotherapy in indoleamine 2,3-dioxygenase-expressing tumors.
Rikke B Holmgaard, Dmitriy Zamarin, +2 authors, Jedd D Wolchok.
EBioMedicine, 2016 May 24; 6. PMID: 27211548    Free PMC article.
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Macrophages mediate gemcitabine resistance of pancreatic adenocarcinoma by upregulating cytidine deaminase.
N Weizman, Y Krelin, +4 authors, Z Gil.
Oncogene, 2013 Sep 03; 33(29). PMID: 23995783
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Inhibition of T cell proliferation by macrophage tryptophan catabolism.
D H Munn, E Shafizadeh, +3 authors, A L Mellor.
J Exp Med, 1999 May 04; 189(9). PMID: 10224276    Free PMC article.
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Direct evidence for rapid and selective induction of tumor neovascular permeability by tumor necrosis factor and a novel derivative, colloidal gold bound tumor necrosis factor.
Jeffrey M Farma, Markus Puhlmann, +4 authors, H Richard Alexander.
Int J Cancer, 2007 Mar 03; 120(11). PMID: 17330231
Macrophages help NK cells to attack tumor cells by stimulatory NKG2D ligand but protect themselves from NK killing by inhibitory ligand Qa-1.
Zhixia Zhou, Cai Zhang, Jian Zhang, Zhigang Tian.
PLoS One, 2012 May 26; 7(5). PMID: 22629344    Free PMC article.
Targeting macrophage priming by polyphyllin VII triggers anti-tumor immunity via STING-governed cytotoxic T-cell infiltration in lung cancer.
Jinglu Yu, Haibin Deng, Zhenye Xu.
Sci Rep, 2020 Dec 09; 10(1). PMID: 33288772    Free PMC article.
Macrophage-Derived CXCL9 and CXCL10 Are Required for Antitumor Immune Responses Following Immune Checkpoint Blockade.
Imran G House, Peter Savas, +17 authors, Paul A Beavis.
Clin Cancer Res, 2019 Oct 23; 26(2). PMID: 31636098
Tumor-infiltrating CD14-positive myeloid cells and CD8-positive T-cells prolong survival in patients with cervical carcinoma.
P J de Vos van Steenwijk, T H Ramwadhdoebe, +8 authors, E S Jordanova.
Int J Cancer, 2013 Jun 07; 133(12). PMID: 23740735
Dihydrotestosterone Increases Cytotoxic Activity of Macrophages on Prostate Cancer Cells via TRAIL.
Geun Taek Lee, Jeong Hyun Kim, +7 authors, Isaac Yi Kim.
Endocrinology, 2019 Jun 12; 160(9). PMID: 31184711    Free PMC article.
Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti-CTLA-4 therapy against melanoma.
Tyler R Simpson, Fubin Li, +11 authors, Sergio A Quezada.
J Exp Med, 2013 Jul 31; 210(9). PMID: 23897981    Free PMC article.
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Safety and efficacy of AMG 820, an anti-colony-stimulating factor 1 receptor antibody, in combination with pembrolizumab in adults with advanced solid tumors.
Albiruni Ra Razak, James M Cleary, +18 authors, Kyriakos P Papadopoulos.
J Immunother Cancer, 2020 Oct 14; 8(2). PMID: 33046621    Free PMC article.
Blockade of tumor necrosis factor alpha signaling in tumor-associated macrophages as a radiosensitizing strategy.
Yuru Meng, Michael A Beckett, +4 authors, Ralph R Weichselbaum.
Cancer Res, 2010 Feb 11; 70(4). PMID: 20145121    Free PMC article.
Close association between Fas ligand (FasL; CD95L)-positive tumor-associated macrophages and apoptotic cancer cells along invasive margin of colorectal carcinoma: a proposal on tumor-host interactions.
Junichi Sugita, Haruo Ohtani, +7 authors, Hiroshi Nagura.
Jpn J Cancer Res, 2002 Apr 03; 93(3). PMID: 11927015    Free PMC article.
Rapid vascular regrowth in tumors after reversal of VEGF inhibition.
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J Clin Invest, 2006 Oct 04; 116(10). PMID: 17016557    Free PMC article.
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Metformin prevents cancer metastasis by inhibiting M2-like polarization of tumor associated macrophages.
Ling Ding, Guikai Liang, +7 authors, Qiaojun He.
Oncotarget, 2015 Oct 27; 6(34). PMID: 26497364    Free PMC article.
Poly(I:C) stimulation is superior than Imiquimod to induce the antitumoral functional profile of tumor-conditioned macrophages.
Akihiro Maeda, Elisabeth Digifico, +2 authors, Paola Allavena.
Eur J Immunol, 2019 Feb 20; 49(5). PMID: 30779113    Free PMC article.
C1q and mannose binding lectin engagement of cell surface calreticulin and CD91 initiates macropinocytosis and uptake of apoptotic cells.
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J Exp Med, 2001 Sep 19; 194(6). PMID: 11560994    Free PMC article.
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Oncology meets immunology: the cancer-immunity cycle.
Daniel S Chen, Ira Mellman.
Immunity, 2013 Jul 31; 39(1). PMID: 23890059
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Anti-PD-L1 Treatment Results in Functional Remodeling of the Macrophage Compartment.
Huizhong Xiong, Stephanie Mittman, +5 authors, Rafael Cubas.
Cancer Res, 2019 Jan 27; 79(7). PMID: 30679180
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Extrinsic Phagocyte-Dependent STING Signaling Dictates the Immunogenicity of Dying Cells.
Jeonghyun Ahn, Tianli Xia, +2 authors, Glen N Barber.
Cancer Cell, 2018 May 01; 33(5). PMID: 29706455    Free PMC article.
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Subcapsular sinus macrophages prevent CNS invasion on peripheral infection with a neurotropic virus.
Matteo Iannacone, E Ashley Moseman, +6 authors, Ulrich H von Andrian.
Nature, 2010 Jun 26; 465(7301). PMID: 20577213    Free PMC article.
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Inhibition of arginase by CB-1158 blocks myeloid cell-mediated immune suppression in the tumor microenvironment.
Susanne M Steggerda, Mark K Bennett, +18 authors, Matthew I Gross.
J Immunother Cancer, 2017 Dec 20; 5(1). PMID: 29254508    Free PMC article.
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Human macrophages and dendritic cells can equally present MART-1 antigen to CD8(+) T cells after phagocytosis of gamma-irradiated melanoma cells.
María Marcela Barrio, Riad Abes, +7 authors, Jean-Luc Teillaud.
PLoS One, 2012 Jul 07; 7(7). PMID: 22768350    Free PMC article.
Autocrine TGFβ Is a Survival Factor for Monocytes and Drives Immunosuppressive Lineage Commitment.
Alba Gonzalez-Junca, Kyla E Driscoll, +8 authors, Mary Helen Barcellos-Hoff.
Cancer Immunol Res, 2018 Dec 13; 7(2). PMID: 30538091    Free PMC article.
PI3K Inhibition Reduces Mammary Tumor Growth and Facilitates Antitumor Immunity and Anti-PD1 Responses.
Jiqing Sai, Philip Owens, +14 authors, Ann Richmond.
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Nature, 2017 Jan 20; 541(7637). PMID: 28102259
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Outcome and prognostic factor analysis of 217 consecutive isolated limb perfusions with tumor necrosis factor-alpha and melphalan for limb-threatening soft tissue sarcoma.
Dirk J Grunhagen, Johannes H W de Wilt, +3 authors, Alexander M M Eggermont.
Cancer, 2006 Mar 17; 106(8). PMID: 16541435
Immunotherapeutic effects of intratumoral nanoplexed poly I:C.
M Angela Aznar, Lourdes Planelles, +13 authors, Ignacio Melero.
J Immunother Cancer, 2019 May 03; 7(1). PMID: 31046839    Free PMC article.
Monocyte-derived macrophages promote breast cancer bone metastasis outgrowth.
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J Exp Med, 2020 Aug 12; 217(11). PMID: 32780802    Free PMC article.
CCL2-CCR2 axis recruits tumor associated macrophages to induce immune evasion through PD-1 signaling in esophageal carcinogenesis.
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Mol Cancer, 2020 Feb 28; 19(1). PMID: 32103760    Free PMC article.
CD47-blocking immunotherapies stimulate macrophage-mediated destruction of small-cell lung cancer.
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Tumour macrophages as potential targets of bisphosphonates.
Thea L Rogers, Ingunn Holen.
J Transl Med, 2011 Oct 19; 9. PMID: 22005011    Free PMC article.
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Antibody-Mediated Blockade of Phosphatidylserine Enhances the Antitumor Effect of Sorafenib in Hepatocellular Carcinomas Xenografts.
Xiaoyun Cheng, Li Li, +3 authors, Xianming Huang.
Ann Surg Oncol, 2016 Feb 06; 23(Suppl 5). PMID: 26847681
Macrophage IL-10 blocks CD8+ T cell-dependent responses to chemotherapy by suppressing IL-12 expression in intratumoral dendritic cells.
Brian Ruffell, Debbie Chang-Strachan, +7 authors, Lisa M Coussens.
Cancer Cell, 2014 Dec 03; 26(5). PMID: 25446896    Free PMC article.
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Tumor-Associated Macrophages in Human Breast, Colorectal, Lung, Ovarian and Prostate Cancers.
Irina Larionova, Gulnara Tuguzbaeva, +5 authors, Julia Kzhyshkowska.
Front Oncol, 2020 Nov 17; 10. PMID: 33194645    Free PMC article.
Podoplanin-Expressing Macrophages Promote Lymphangiogenesis and Lymphoinvasion in Breast Cancer.
Paweł Bieniasz-Krzywiec, Rosa Martín-Pérez, +14 authors, Massimiliano Mazzone.
Cell Metab, 2019 Aug 27; 30(5). PMID: 31447322
Cytokine-Coding Oncolytic Adenovirus TILT-123 Is Safe, Selective, and Effective as a Single Agent and in Combination with Immune Checkpoint Inhibitor Anti-PD-1.
Riikka Havunen, Riikka Kalliokoski, +5 authors, Akseli Hemminki.
Cells, 2021 Jan 31; 10(2). PMID: 33513935    Free PMC article.
Toll-like Receptor Signaling Rewires Macrophage Metabolism and Promotes Histone Acetylation via ATP-Citrate Lyase.
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Immunity, 2019 Dec 19; 51(6). PMID: 31851905
UC-1V150, a potent TLR7 agonist capable of activating macrophages and potentiating mAb-mediated target cell deletion.
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Scand J Immunol, 2018 Apr 19; 87(6). PMID: 29667229
Tumor microenvironment remodeling by an engineered oncolytic adenovirus results in improved outcome from PD-L1 inhibition.
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Oncoimmunology, 2020 Sep 15; 9(1). PMID: 32923123    Free PMC article.
Breast Phyllodes Tumors Recruit and Repolarize Tumor-Associated Macrophages via Secreting CCL5 to Promote Malignant Progression, Which Can Be Inhibited by CCR5 Inhibition Therapy.
Yan Nie, Hongyan Huang, +13 authors, Hai Hu.
Clin Cancer Res, 2019 Mar 21; 25(13). PMID: 30890553
Tumoricidal effects of activated macrophages in a mouse model of chronic lymphocytic leukemia.
Qing-Li Wu, Ilia N Buhtoiarov, +2 authors, Erik A Ranheim.
J Immunol, 2009 May 21; 182(11). PMID: 19454672    Free PMC article.
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J Immunol, 2000 Jan 07; 164(2). PMID: 10623821
Intratumoral macrophages contribute to epithelial-mesenchymal transition in solid tumors.
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Tissue-resident macrophages provide a pro-tumorigenic niche to early NSCLC cells.
María Casanova-Acebes, Erica Dalla, +24 authors, Miriam Merad.
Nature, 2021 Jun 18; 595(7868). PMID: 34135508    Free PMC article.
A paracrine loop between tumor cells and macrophages is required for tumor cell migration in mammary tumors.
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Cancer Res, 2004 Oct 07; 64(19). PMID: 15466195
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MerTK as a therapeutic target in glioblastoma.
Jing Wu, Lauren N Frady, +12 authors, C Ryan Miller.
Neuro Oncol, 2017 Jun 13; 20(1). PMID: 28605477    Free PMC article.
T cell-induced CSF1 promotes melanoma resistance to PD1 blockade.
Natalie J Neubert, Martina Schmittnaegel, +18 authors, Daniel E Speiser.
Sci Transl Med, 2018 Apr 13; 10(436). PMID: 29643229    Free PMC article.
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Macrophage-derived CCL22 promotes an immunosuppressive tumor microenvironment via IL-8 in malignant pleural effusion.
Dong Wang, Li Yang, +8 authors, Yi Zhang.
Cancer Lett, 2019 Apr 01; 452. PMID: 30928379
Interferon-Gamma at the Crossroads of Tumor Immune Surveillance or Evasion.
Flávia Castro, Ana Patrícia Cardoso, +2 authors, Maria José Oliveira.
Front Immunol, 2018 May 22; 9. PMID: 29780381    Free PMC article.
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Clodronate-liposome-mediated depletion of tumour-associated macrophages: a new and highly effective antiangiogenic therapy approach.
S M Zeisberger, B Odermatt, +3 authors, R A Schwendener.
Br J Cancer, 2006 Jul 13; 95(3). PMID: 16832418    Free PMC article.
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Pembrolizumab for Early Triple-Negative Breast Cancer.
Peter Schmid, Javier Cortes, +19 authors, KEYNOTE-522 Investigators.
N Engl J Med, 2020 Feb 27; 382(9). PMID: 32101663
The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors.
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Proc Natl Acad Sci U S A, 2012 Mar 28; 109(17). PMID: 22451913    Free PMC article.
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Regression of established AB1 murine mesothelioma induced by peritumoral injections of CpG oligodeoxynucleotide either alone or in combination with poly(I:C) and CD40 ligand plasmid DNA.
Geoffrey W Stone, Suzanne Barzee, +3 authors, Richard S Kornbluth.
J Thorac Oncol, 2009 Jun 25; 4(7). PMID: 19550243
Tumor-associated macrophages and response to 5-fluorouracil adjuvant therapy in stage III colorectal cancer.
Alberto Malesci, Paolo Bianchi, +13 authors, Luigi Laghi.
Oncoimmunology, 2017 Dec 07; 6(12). PMID: 29209561    Free PMC article.
TLR7/8-agonist-loaded nanoparticles promote the polarization of tumour-associated macrophages to enhance cancer immunotherapy.
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Nat Biomed Eng, 2019 Apr 25; 2(8). PMID: 31015631    Free PMC article.
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Low dose radiation primed iNOS + M1macrophages modulate angiogenic programming of tumor derived endothelium.
Vinod Nadella, Sandhya Singh, +6 authors, Hridayesh Prakash.
Mol Carcinog, 2018 Jul 24; 57(11). PMID: 30035346    Free PMC article.
Macrophage-activating factors from different T cell clones induce distinct macrophage functions.
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J Immunol, 1983 Aug 01; 131(2). PMID: 6190940
M-CSF and GM-CSF Receptor Signaling Differentially Regulate Monocyte Maturation and Macrophage Polarization in the Tumor Microenvironment.
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Cancer Res, 2015 Nov 18; 76(1). PMID: 26573801
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Cetuximab enhances the anti-tumor function of macrophages in an IL-6 dependent manner.
Yahui Zhao, Xianghe Liu, +4 authors, Hongxia Zhu.
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Biomater Sci, 2019 Jun 25; 7(8). PMID: 31233057
The role of indoleamine 2,3-dioxygenase (IDO) in immune tolerance: focus on macrophage polarization of THP-1 cells.
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Cell Immunol, 2014 Apr 12; 289(1-2). PMID: 24721110
Targeting Phosphatidylserine Enhances the Anti-tumor Response to Tumor-Directed Radiation Therapy in a Preclinical Model of Melanoma.
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Cell Rep, 2021 Jan 14; 34(2). PMID: 33440157    Free PMC article.
Injectable polypeptide hydrogel for dual-delivery of antigen and TLR3 agonist to modulate dendritic cells in vivo and enhance potent cytotoxic T-lymphocyte response against melanoma.
Huijuan Song, Pingsheng Huang, +4 authors, Weiwei Wang.
Biomaterials, 2018 Jan 13; 159. PMID: 29324304
Autocrine IL-10 functions as a rheostat for M1 macrophage glycolytic commitment by tuning nitric oxide production.
Walter A Baseler, Luke C Davies, +5 authors, Daniel W McVicar.
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CSF1R signaling blockade stanches tumor-infiltrating myeloid cells and improves the efficacy of radiotherapy in prostate cancer.
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M2 macrophages are more resistant than M1 macrophages following radiation therapy in the context of glioblastoma.
Marine M Leblond, Elodie A Pérès, +7 authors, Samuel Valable.
Oncotarget, 2017 Oct 27; 8(42). PMID: 29069812    Free PMC article.
Expression of vascular endothelial growth factor by macrophages is up-regulated in poorly vascularized areas of breast carcinomas.
J S Lewis, R J Landers, +2 authors, C E Lewis.
J Pathol, 2000 Sep 27; 192(2). PMID: 11004690
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Cancer Res, 2000 Nov 04; 60(20). PMID: 11059783
Synergistic activation of macrophages via CD40 and TLR9 results in T cell independent antitumor effects.
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J Immunol, 2005 Dec 21; 176(1). PMID: 16365423
Anti-PlGF inhibits growth of VEGF(R)-inhibitor-resistant tumors without affecting healthy vessels.
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Cell, 2007 Nov 06; 131(3). PMID: 17981115
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Analysis of multiple biomarkers shows that lymphoma-associated macrophage (LAM) content is an independent predictor of survival in follicular lymphoma (FL).
Pedro Farinha, Hamid Masoudi, +7 authors, Randy D Gascoyne.
Blood, 2005 Jun 04; 106(6). PMID: 15933054
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Prognostic and predictive role of tumour-associated macrophages in HER2 positive breast cancer.
Tiia J Honkanen, Antti Tikkanen, +3 authors, Jussi P Koivunen.
Sci Rep, 2019 Jul 31; 9(1). PMID: 31358801    Free PMC article.
Anti-CD47 antibody-mediated phagocytosis of cancer by macrophages primes an effective antitumor T-cell response.
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Proc Natl Acad Sci U S A, 2013 May 22; 110(27). PMID: 23690610    Free PMC article.
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Loss of transforming growth factor-beta signaling in mammary fibroblasts enhances CCL2 secretion to promote mammary tumor progression through macrophage-dependent and -independent mechanisms.
Stacey L Hembruff, Iman Jokar, Li Yang, Nikki Cheng.
Neoplasia, 2010 May 11; 12(5). PMID: 20454514    Free PMC article.
Functional CD169 on Macrophages Mediates Interaction with Dendritic Cells for CD8+ T Cell Cross-Priming.
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Cell Rep, 2018 Feb 10; 22(6). PMID: 29425504
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Targeting tumor-associated macrophages with anti-CSF-1R antibody reveals a strategy for cancer therapy.
Carola H Ries, Michael A Cannarile, +24 authors, Dominik Rüttinger.
Cancer Cell, 2014 Jun 06; 25(6). PMID: 24898549
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cIAP1/2 antagonism eliminates MHC class I-negative tumors through T cell-dependent reprogramming of mononuclear phagocytes.
Kevin Roehle, Li Qiang, +26 authors, Stephanie K Dougan.
Sci Transl Med, 2021 May 21; 13(594). PMID: 34011631    Free PMC article.
Functional characterization of a STAT3-dependent dendritic cell-derived CD14+ cell population arising upon IL-10-driven maturation.
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Oncoimmunology, 2013 Jun 05; 2(4). PMID: 23734330    Free PMC article.
Single-Cell Transcriptomics of Human and Mouse Lung Cancers Reveals Conserved Myeloid Populations across Individuals and Species.
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Active secretion of CXCL10 and CCL5 from colorectal cancer microenvironments associates with GranzymeB+ CD8+ T-cell infiltration.
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Crosstalk between cancer cells and tumor associated macrophages is required for mesenchymal circulating tumor cell-mediated colorectal cancer metastasis.
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Mol Cancer, 2019 Apr 01; 18(1). PMID: 30927925    Free PMC article.
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Alternative M2 activation of Kupffer cells by PPARdelta ameliorates obesity-induced insulin resistance.
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Cell Metab, 2008 Jun 05; 7(6). PMID: 18522831    Free PMC article.
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Hedgehog-induced PD-L1 on tumor-associated macrophages is critical for suppression of tumor-infiltrating CD8+ T cell function.
Amy J Petty, Rui Dai, +5 authors, Yiping Yang.
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CCL5 promotes breast cancer recurrence through macrophage recruitment in residual tumors.
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Elife, 2019 Apr 17; 8. PMID: 30990165    Free PMC article.
A nanoparticle-based approach to improve the outcome of cancer active immunotherapy with lipopolysaccharides.
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Combination of CD40 Agonism and CSF-1R Blockade Reconditions Tumor-Associated Macrophages and Drives Potent Antitumor Immunity.
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Targeting Lymph Node Sinus Macrophages to Inhibit Lymph Node Metastasis.
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Targeted disruption of the mouse colony-stimulating factor 1 receptor gene results in osteopetrosis, mononuclear phagocyte deficiency, increased primitive progenitor cell frequencies, and reproductive defects.
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