Macrophages: Key orchestrators of a tumor microenvironment defined by therapeutic resistance.

Macrophages have emerged as promising therapeutic targets in cancer. Within tumor tissue, macrophages foster tumor development, invasion, and metastasis. As the phenotype of macrophages is inherently pliable and dependent on cues received from the surrounding microenvironment, macrophages co-evolve with malignant and other non-malignant cells during cancer progression. In doing so, they establish a microenvironment that is therapeutically resistant and thwarts the productivity of T cell immunosuveillance. Strategies designed to deplete, inhibit, or redirect macrophages with anti-tumor activity are being explored to reverse the pro-tumor properties of macrophages that are commonly observed in cancer. In this review, we discuss our current understanding of the mechanisms that regulate macrophage recruitment to tumors, their impact on the tumor microenvironment, and their promise as therapeutic targets for improving the efficacy of cytotoxic- and immune-based therapies.

• Publication year

  2017

• Venue

  Molecular Immunology

• Publication date

  2017-12-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/j.molimm.2017.12.003PMID 29273393PMCID PMC6008174
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Disrupting the CD47-SIRPα anti-phagocytic axis by a humanized anti-CD47 antibody is an efficacious treatment for malignant pediatric brain tumors

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• Class IIa HDAC inhibition reduces breast tumours and metastases through anti-tumour macrophages

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• Cancer immunotherapy: activating innate and adaptive immunity through CD40 agonists

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• IL6 Receptor Blockade Enhances Chemotherapy Efficacy in Pancreatic Ductal Adenocarcinoma

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• Tissue-Resident Macrophages in Pancreatic Ductal Adenocarcinoma Originate from Embryonic Hematopoiesis and Promote Tumor Progression.

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• Phagocytosis imprints heterogeneity in tissue-resident macrophages

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• Colony-Stimulating Factor 1 Receptor Blockade Inhibits Tumor Growth by Altering the Polarization of Tumor-Associated Macrophages in Hepatocellular Carcinoma

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• Exosomes derived from hypoxic epithelial ovarian cancer deliver microRNA-940 to induce macrophage M2 polarization.

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• Depletion of Tumor-Associated Macrophages with a CSF-1R Kinase Inhibitor Enhances Antitumor Immunity and Survival Induced by DC Immunotherapy

  2017influential reference
• Functio Laesa: Cancer Inflammation and Therapeutic Resistance.

  2017influential reference
• STAT3 and STAT6 Signaling Pathways Synergize to Promote Cathepsin Secretion from Macrophages via IRE1α Activation.

  2016cited by this paper
• Targeting tumour-associated macrophages with CCR2 inhibition in combination with FOLFIRINOX in patients with borderline resectable and locally advanced pancreatic cancer: a single-centre, open-label, dose-finding, non-randomised, phase 1b trial.

  2016cited by this paper
• Targeting Suppressive Myeloid Cells Potentiates Checkpoint Inhibitors to Control Spontaneous Neuroblastoma

  2016influential reference
• The impact of hypoxia on tumor-associated macrophages.

  2016cited by this paper
• Mesenchymal Stem Cells Promote Pancreatic Tumor Growth by Inducing Alternative Polarization of Macrophages12

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• Targeting the CCL2-CCR2 signaling axis in cancer metastasis

  2016cited by this paper
• IFNγ and CCL2 Cooperate to Redirect Tumor-Infiltrating Monocytes to Degrade Fibrosis and Enhance Chemotherapy Efficacy in Pancreatic Carcinoma.

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• Timing of CSF-1/CSF-1R signaling blockade is critical to improving responses to CTLA-4 based immunotherapy

  2016influential reference
• Succinate Dehydrogenase Supports Metabolic Repurposing of Mitochondria to Drive Inflammatory Macrophages.

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• Tumor macrophages are pivotal constructors of tumor collagenous matrix

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• PI3Kγ is a molecular switch that controls immune suppression

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• Tie2 Expression on Macrophages Is Required for Blood Vessel Reconstruction and Tumor Relapse after Chemotherapy.

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• Tumor-Derived CCL2 Mediates Resistance to Radiotherapy in Pancreatic Ductal Adenocarcinoma

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• Targeting Focal Adhesion Kinase Renders Pancreatic Cancers Responsive to Checkpoint Immunotherapy

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• Tumoral Immune Cell Exploitation in Colorectal Cancer Metastases Can Be Targeted Effectively by Anti-CCR5 Therapy in Cancer Patients.

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• MFHAS1 promotes colorectal cancer progress by regulating polarization of tumor-associated macrophages via STAT6 signaling pathway

  2016cited by this paper
• Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver

  2015cited by this paper
• CSF1/CSF1R blockade reprograms tumor-infiltrating macrophages and improves response to T-cell checkpoint immunotherapy in pancreatic cancer models.

  2015cited by this paper
• High and low molecular weight hyaluronic acid differentially influence macrophage activation.

  2015cited by this paper
• Opposite Effects of M1 and M2 Macrophage Subtypes on Lung Cancer Progression

  2015cited by this paper
• Signal Transducer and Activator of Transcription 3, Mediated Remodeling of the Tumor Microenvironment Results in Enhanced Tumor Drug Delivery in a Mouse Model of Pancreatic Cancer.

  2015cited by this paper
• Physical and mechanical regulation of macrophage phenotype and function

  2015cited by this paper
• Phase I clinical study of the toll-like receptor 9 agonist MGN1703 in patients with metastatic solid tumours.

  2015cited by this paper
• CD47 Blockade Triggers T cell-mediated Destruction of Immunogenic Tumors

  2015cited by this paper
• Macrophages eat cancer cells using their own calreticulin as a guide: Roles of TLR and Btk

  2015cited by this paper
• Mutant KRAS-induced expression of ICAM-1 in pancreatic acinar cells causes attraction of macrophages to expedite the formation of precancerous lesions.

  2015cited by this paper
• Exclusion of T Cells From Pancreatic Carcinomas in Mice is Regulated by Ly6C low F4/80 + Extra-tumor Macrophages

  2015cited by this paper
• Exclusion of T Cells From Pancreatic Carcinomas in Mice Is Regulated by Ly6C(low) F4/80(+) Extratumoral Macrophages.

  2015cited by this paper
• Managing Cytokine Release Syndrome Associated With Novel T Cell-Engaging Therapies

  2014cited by this paper
• Molecular Pathways Molecular Pathways : Connecting Fibrosis and Solid Tumor Metastasis

  2014cited by this paper
• Metabolic Reprograming in Macrophage Polarization

  2014cited by this paper
• Targeting tumor-associated macrophages with anti-CSF-1R antibody reveals a strategy for cancer therapy.

  2014cited by this paper
• Origin and functions of tissue macrophages.

  2014influential reference
• Tumor-Associated Macrophages Are a Useful Biomarker to Predict Recurrence After Surgical Resection of Nonfunctional Pancreatic Neuroendocrine Tumors

  2014cited by this paper
• Functional polarization of tumour-associated macrophages by tumour-derived lactic acid

  2014influential reference
• Rac2 Controls Tumor Growth, Metastasis and M1-M2 Macrophage Differentiation In Vivo

  2014influential reference
• Macrophage activation and polarization: nomenclature and experimental guidelines.

  2014cited by this paper
• The cellular and molecular origin of tumor-associated macrophages

  2014cited by this paper
• Immune Escape Mechanisms as a Guide for Cancer Immunotherapy

  2014cited by this paper
• Head and neck cancer relapse after chemoradiotherapy correlates with CD163+ macrophages in primary tumour and CD11b+ myeloid cells in recurrences

  2014cited by this paper
• The M1 and M2 paradigm of macrophage activation: time for reassessment

  2014influential reference
• Tissue-resident macrophages

  2013cited by this paper
• Critical Role of Transforming Growth Factor Beta in Different Phases of Wound Healing

  2013cited by this paper
• A Phase I Study of an Agonist CD40 Monoclonal Antibody (CP-870,893) in Combination with Gemcitabine in Patients with Advanced Pancreatic Ductal Adenocarcinoma

  2013cited by this paper
• Impeding macrophage entry into hypoxic tumor areas by Sema3A/Nrp1 signaling blockade inhibits angiogenesis and restores antitumor immunity.

  2013cited by this paper
• Recruitment of a myeloid cell subset (CD11b/Gr1mid) via CCL2/CCR2 promotes the development of colorectal cancer liver metastasis *

  2013cited by this paper
• differentiation into tumor-associated macrophage-like cells Tumor-associated leukemia inhibitory factor and IL-6 skew monocyte

  2013cited by this paper
• CSF-1R inhibition alters macrophage polarization and blocks glioma progression

  2013cited by this paper
• The roles of TGFβ in the tumour microenvironment

  2013influential reference
• Minimal differentiation of classical monocytes as they survey steady-state tissues and transport antigen to lymph nodes.

  2013cited by this paper
• Lung Collagens Perpetuate Pulmonary Fibrosis via CD204 and M2 Macrophage Activation

  2013cited by this paper
• Harnessing the antitumor potential of macrophages for cancer immunotherapy

  2013influential reference
• Modulation of macrophage phenotype by cell shape

  2013cited by this paper
• Engineered SIRPα Variants as Immunotherapeutic Adjuvants to Anticancer Antibodies

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• Role of macrophage targeting in the antitumor activity of trabectedin.

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• Inflammatory Monocyte Mobilization Decreases Patient Survival in Pancreatic Cancer: A Role for Targeting the CCL2/CCR2 Axis

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• Targeting tumor-infiltrating macrophages decreases tumor-initiating cells, relieves immunosuppression, and improves chemotherapeutic responses.

  2013influential reference
• Mechanisms of fibrosis: therapeutic translation for fibrotic disease

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• Enzymatic targeting of the stroma ablates physical barriers to treatment of pancreatic ductal adenocarcinoma.

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• Deficiency of the macrophage growth factor CSF-1 disrupts pancreatic neuroendocrine tumor development

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• Macrophage plasticity and polarization: in vivo veritas.

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• The CD47-SIRPα pathway in cancer immune evasion and potential therapeutic implications.

  2012influential reference
• The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors

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• Protective and pathogenic functions of macrophage subsets

  2011cited by this paper
• Leukocyte complexity predicts breast cancer survival and functionally regulates response to chemotherapy.

  2011cited by this paper
• A Critical Role for Macrophages in Promotion of Urethane-Induced Lung Carcinogenesis

  2011cited by this paper
• Stat3/Socs3 activation by IL-6 transsignaling promotes progression of pancreatic intraepithelial neoplasia and development of pancreatic cancer.

  2011cited by this paper
• Hallmarks of cancer: the next generation.

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• The Two Faces of Interferon-γ in Cancer

  2011cited by this paper
• CCL2 recruits inflammatory monocytes to facilitate breast tumor metastasis

  2011cited by this paper
• STAT3 plays a critical role in KRAS-induced pancreatic tumorigenesis.

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• Programmed cell removal: a new obstacle in the road to developing cancer

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• Monocyte recruitment during infection and inflammation

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• CD40 Agonists Alter Tumor Stroma and Show Efficacy Against Pancreatic Carcinoma in Mice and Humans

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• Targeting the ANG2/TIE2 axis inhibits tumor growth and metastasis by impairing angiogenesis and disabling rebounds of proangiogenic myeloid cells.

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• Repeated TLR9 stimulation results in macrophage activation syndrome-like disease in mice.

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• Tumour-infiltrating macrophages and clinical outcome in breast cancer

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• Cancer-Associated Fibroblasts Are Activated in Incipient Neoplasia to Orchestrate Tumor-Promoting Inflammation in an NF-kappaB-Dependent Manner.

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• Dynamic interplay between the collagen scaffold and tumor evolution.

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• Macrophage diversity enhances tumor progression and metastasis.

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• Cancer esearch oenvironment and Immunology luronan Deficiency in Tumor Stroma Impairs Macrophage R fficking and Tumor Neovascularization

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• Alternative activation of macrophages: mechanism and functions.

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• Inhibition of Hedgehog Signaling Enhances Delivery of Chemotherapy in a Mouse Model of Pancreatic Cancer

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• CCL2 and Interleukin-6 Promote Survival of Human CD11b+ Peripheral Blood Mononuclear Cells and Induce M2-type Macrophage Polarization*

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• Expression of the macrophage antigen CD163 in rectal cancer cells is associated with early local recurrence and reduced survival time

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• STATs in cancer inflammation and immunity: a leading role for STAT3

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• Activated monocytes in peritumoral stroma of hepatocellular carcinoma foster immune privilege and disease progression through PD-L1

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• Stat6 Signaling Suppresses VLA-4 Expression by CD8+ T Cells and Limits Their Ability to Infiltrate Tumor Lesions In Vivo1

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• Toll-like receptor 9 (TLR9) agonists in the treatment of cancer

  2008influential reference

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• Shaping Immunotherapy Through the Tumor Microenvironment: Translational Perspectives.

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• From Combination Early Detection to Multicancer Testing: Shifting Cancer Care toward Proactive Prevention and Interception

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• Hsa-miR-21 promoted the progression of lung adenocarcinoma by regulating LRIG1 expression

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• Tumor-associated-fibrosis and active collagen-CD44 axis characterize a poor-prognosis subtype of gastric cancer and contribute to tumor immunosuppression

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• Nanomedicine in Immunotherapy for Non‐Small Cell Lung Cancer: Applications and Perspectives

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• Immune cell-based therapies for solid tumors, current challenges and therapeutic advances

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• Progressions of the correlation between lipid metabolism and immune infiltration characteristics in gastric cancer and identification of BCHE as a potential biomarker

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• Metabolic Reprogramming of Immune Cells in the Tumor Microenvironment

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• Exploring the Mechanisms and Current Status of Acupuncture in Alleviating Tumor Metabolism and Associated Diseases: Insights from the Central Nervous System and Immune Microenvironment.

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• Cancer associated fibroblast secreted miR-432-5p targets CHAC1 to inhibit ferroptosis and promote acquired chemoresistance in prostate cancer

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• Macrophages as targets in hepatocellular carcinoma therapy.

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• Autotaxin–lysolipid signaling suppresses a CCL11–eosinophil axis to promote pancreatic cancer progression

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• Bacteria and macrophages in the tumor microenvironment

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• Targeting cholesterol metabolism in Cancer: From molecular mechanisms to therapeutic implications.

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• Bridging the gap between clear cell renal cell carcinoma and cutaneous melanoma: the role of SCARB1 in dysregulated cholesterol metabolism

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• Key role of exosomes derived from M2 macrophages in maintaining cancer cell stemness (Review)

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• A role for platelets in metabolic reprogramming of tumor-associated macrophages

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• Polarization of Cancer-Associated Macrophages Maneuver Neoplastic Attributes of Pancreatic Ductal Adenocarcinoma

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• Unraveling the significance of exosomal circRNAs in cancer therapeutic resistance

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• From the Catastrophic Objective Irreproducibility of Cancer Research and Unavoidable Failures of Molecular Targeted Therapies to the Sparkling Hope of Supramolecular Targeted Strategies

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• The Role of Osteopontin in Tumor Progression Through Tumor-Associated Macrophages

  2022cites this paper
• Identify potential prognostic indicators and tumor-infiltrating immune cells in pancreatic adenocarcinoma

  2022cites this paper
• Tumor hijacks macrophages and microbiota through extracellular vesicles

  2022cites this paper
• Valproic acid counteracts polycyclic aromatic hydrocarbons (PAHs)-induced tumorigenic effects by regulating the polarization of macrophages.

  2022cites this paper
• Tumor Infiltrating Myeloid Cells Confer de novo Resistance to PD-L1 Blockade through EMT-stromal and Tgf-beta Dependent Mechanisms.

  2022cites this paper
• Tumor Microenvironment in Pancreatic Cancer Pathogenesis and Therapeutic Resistance.

  2022cites this paper
• Boolean modeling reveals that cyclic attractors in macrophage polarization serve as reservoirs of states to balance external perturbations from the tumor microenvironment

  2022cites this paper
• Developing a 3D B Cell Lymphoma Culture System to Model Antibody Therapy

  2021cites this paper
• Tumor-associated macrophages in lung carcinoma: From mechanism to therapy.

  2021cites this paper
• Payload Delivery: Engineering Immune Cells to Disrupt the Tumour Microenvironment

  2021cites this paper
• circRNAs: Insight Into Their Role in Tumor-Associated Macrophages

  2021cites this paper
• Tumor associated macrophage and microbe: the potential targets of tumor vaccine delivery.

  2021cites this paper
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  2021cites this paper
• Low expression of endoplasmic reticulum stress-related gene SERP1 is associated with poor prognosis and immune infiltration in skin cutaneous melanoma

  2021cites this paper
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  2020cites this paper
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  2020cites this paper
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• Macrophage-derived exosomes in cancers: Biogenesis, functions and therapeutic applications.

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• Macrophages potentiate STAT3 signaling in skeletal muscles and regulate pancreatic cancer cachexia.

  2020cites this paper
• Cellular determinants and therapeutic implications of inflammation in pancreatic cancer.

  2019cites this paper
• Circular RNAs in drug resistant tumors.

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• YAP and TAZ: a signalling hub of the tumour microenvironment

  2019cites this paper
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  2019cites this paper
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