• R03 EB028605 NIBIB NIH HHS
• T32 HL116270 NHLBI NIH HHS

• granuloma
• macrophages
• monocyte development
• mycobacteria
• tissue immunity
• tissue niche

• Humans
• Macrophages/immunology
• Macrophages/metabolism
• Macrophages/microbiology
• Macrophages/cytology
• Cell Differentiation/immunology
• Animals
• Mycobacterium Infections/immunology
• Mycobacterium Infections/metabolism
• Mycobacterium Infections/microbiology
• Host-Pathogen Interactions/immunology
• Adaptation, Physiological
• Mycobacterium tuberculosis/immunology
• Mycobacterium/immunology

• Actin-related protein 2/3 complex
• Cell proliferation
• Immune microenvironment
• Prognostic biomarkers
• Renal cell carcinoma

• Xenograft Model Antitumor Assays
• Mice, Nude
• Cell Proliferation/genetics
• Apoptosis/genetics
• Carcinoma, Renal Cell/drug therapy
• Carcinoma, Renal Cell/genetics
• Carcinoma, Renal Cell/mortality
• Carcinoma, Renal Cell/pathology
• Kidney Neoplasms/drug therapy
• Kidney Neoplasms/genetics
• Kidney Neoplasms/mortality
• Kidney Neoplasms/pathology
• Prognosis
• Actin-Related Protein 2-3 Complex/analysis
• Actin-Related Protein 2-3 Complex/genetics
• Actin-Related Protein 2-3 Complex/metabolism
• Tumor Microenvironment/genetics
• Tumor Microenvironment/immunology
• Drug Resistance, Neoplasm/genetics
• Gene Expression Regulation, Neoplastic/immunology
• Gene Knockdown Techniques
• Biomarkers, Tumor
• Gene Expression Profiling
• Follow-Up Studies
• Kidney/pathology
• Cell Line
• Humans
• Male
• Animals
• Mice
• Mice, Inbred BALB C
• Female
• Middle Aged
• Aged
• Kaplan-Meier Estimate

• cancer-related inflammation
• hypoxia
• metabolism
• tumor micro-environment
• tumor-associated macrophages

• Tumor Microenvironment/immunology
• Humans
• Neoplasms/immunology
• Neoplasms/pathology
• Neoplasms/metabolism
• Stress, Physiological
• Animals
• Signal Transduction

• NET-2016-02361632 Ministero della Salute
• FIRC-AIRC fellowship for Italy for Aldo Ummarino Italian Association for Cancer Research

• ethanol
• ethanol dehydrogenase
• fungal infection
• innate immunity
• nematophagous fungi
• pathogen recognition

• MOST | National Natural Science Foundation of China (NSFC)
• 云南省科学技术厅 | Applied Basic Research Key Project of Yunnan (Applied Basic Research Key Project of Yunnan Province)
• Ten Thousand Talent Plans for Young Top-notch Talents of Yunnan Province (云南省万人计)
• Science and technology special project from southwest united graduate school of Yunnan Province
• Special fund of the Yunnan University "Double First-Class" construction

• Mice
• Animals
• Aortic Aneurysm, Abdominal/etiology
• Aortic Aneurysm, Abdominal/pathology
• Mice, Inbred C57BL
• Disease Models, Animal

• R01 CA273925 NCI NIH HHS
• R01 HL149946 NHLBI NIH HHS
• R01 HL133669 NHLBI NIH HHS
• Office of Extramural Research, National Institutes of Health

• Ischemic stroke
• Microglia
• Monocyte-derived macrophages
• Phagocytes
• Phagocytosis
• Phenotype

• Animals
• Brain/metabolism
• Brain Ischemia/metabolism
• Mice
• Mice, Inbred C57BL
• Microglia/metabolism
• Monocytes/metabolism
• Phagocytosis
• Phenotype
• Stroke/metabolism

• R01 NS095359 NINDS NIH HHS
• R01 NS111568 NINDS NIH HHS
• S10 OD028547 NIH HHS
• National Institutes of Health grants
• NIH S10 shared Instrumentation Grant

• ATP release
• HIF-1α
• Hypoxia
• Purinergic receptors
• ROS

• Cancer-associated fibroblasts
• ECM
• Immunotherapies
• Metastasis
• Tumor microenvironment
• Tumor-associated macrophages

• Immune landscape
• Microenvironment
• Mutational landscape
• Salivary gland carcinoma

• Head and Neck Neoplasms
• Humans
• Molecular Targeted Therapy
• Mutation
• Salivary Gland Neoplasms/genetics
• Salivary Gland Neoplasms/therapy
• Tumor Microenvironment

Mitochondria are considered to be the powerhouse of the cell. Normal functioning of the mitochondria is not only essential for cellular energy production but also for several immunomodulatory processes. Macrophages operate in metabolic niches and rely on rapid adaptation to specific metabolic conditions such as hypoxia, nutrient limitations, or reactive oxygen species to neutralize pathogens. In this regard, the fast reprogramming of mitochondrial metabolism is indispensable to provide the cells with the necessary energy and intermediates to efficiently mount the inflammatory response. Moreover, mitochondria act as a physical scaffold for several proteins involved in immune signaling cascades and their dysfunction is immediately associated with a dampened immune response. In this review, we put special focus on mitochondrial function in macrophages and highlight how mitochondrial metabolism is involved in macrophage activation.

• Itaconic acid
• Macrophages
• Metabolism
• Mitochondira

Painful vaso-occlusive crisis (VOC) remains the most common reason for presenting to the Emergency Department and hospitalization in patients with sickle cell disease (SCD). Although two new agents have been approved by the Food and Drug Administration for treating SCD, they both target to reduce the frequency of VOC. Results from studies investigating various approaches to treat and shorten VOC have so far been generally disappointing. In this paper, we will summarize the complex pathophysiology and downstream events of VOC and discuss the likely reasons for the disappointing results using monotherapy. We will put forward the rationale for exploring some of the currently available agents to either protect erythrocytes un-involved in the hemoglobin polymerization process from sickling induced by the secondary events, or a multipronged combination approach that targets the complex downstream pathways of VOC.

• Downstream events
• Secondary vaso-occlusive crisis
• Sickle cell disease
• Treatment strategies

• acute inflammation
• chronic inflammation

• This work was supported by the University of Central Florida, Space Research Institute award (UCF01-0000409590) provided to E. Moore and J.B. Allen.

• Polyamines
• braf inhibition
• cxcr4
• difluoromethylornithine
• transport inhibitor

• Diabetes
• amputation
• cell therapy
• diabetic foot ulceration
• peripheral arterial disease
• revascularization

• Amputation, Surgical
• Diabetes Mellitus
• Diabetic Foot/complications
• Diabetic Foot/diagnosis
• Diabetic Foot/epidemiology
• Foot Ulcer
• Humans
• Ischemia
• Peripheral Arterial Disease/complications
• Peripheral Arterial Disease/epidemiology
• Peripheral Arterial Disease/therapy

• tumor immunotherapy
• tumor microenvironment
• tumor-associated macrophages (TAMs)

During pregnancy, the mother’s immune system has to tolerate the persistence of paternal alloantigens without affecting the anti-infectious immune response. Consequently, several mechanisms aimed at preventing allograft rejection, occur during a pregnancy. In fact, the early stages of pregnancy are characterized by the correct balance between inflammation and immune tolerance, in which proinflammatory cytokines contribute to both the remodeling of tissues and to neo-angiogenesis, thus, favoring the correct embryo implantation. In addition to the creation of a microenvironment able to support both immunological privilege and angiogenesis, the trophoblast invades normal tissues by sharing the same behavior of invasive tumors. Next, the activation of an immunosuppressive phase, characterized by an increase in the number of regulatory T (Treg) cells prevents excessive inflammation and avoids fetal immuno-mediated rejection. When these changes do not occur or occur incompletely, early pregnancy failure follows. All these events are characterized by an increase in different growth factors and cytokines, among which one of the most important is the angiogenic growth factor, namely placental growth factor (PlGF). PlGF is initially isolated from the human placenta. It is upregulated during both pregnancy and inflammation. In this review, we summarize current knowledge on the immunomodulatory effects of PlGF during pregnancy, warranting that both innate and adaptive immune cells properly support the early events of implantation and placental development. Furthermore, we highlight how an alteration of the immune response, associated with PlGF imbalance, can induce a hypertensive state and lead to the pre-eclampsia (PE).

• Flt-1/VEGFR1
• PlGF
• immune modulation
• pregnancy

• Chronic traumatic encephalopathy
• Immunohistochemistry
• Inflammation
• Microglia
• Traumatic brain injury

• hypoxia
• ischemia
• microglia
• monocyte-derived macrophages
• phagocytosis

• epigenetic regulation
• fatty acid oxidation
• glycolysis
• histones
• metabolism
• methylation
• reprogramming
• transcription factors
• tumor
• tumor-associated macrophages

Traumatic brain injury is among the leading causes of death in individuals under 45 years of age. However, since trauma mechanisms and survival times differ enormously, the exact mechanisms leading to the primary and secondary injury and eventually to death after traumatic brain injury (TBI) remain unclear. Several studies showed the versatile functions of microglia, the innate macrophages of the brain, following a TBI. Earlier being characterized as rather neurotoxic, neuroprotective capacities were recently demonstrated, therefore, making microglia one of the key players following TBI. Especially in cases with only short survival times, immediate microglial reactions are of great forensic interest in questions of wound age estimation. Using standardized immunohistochemical methods, we examined 8 cases which died causatively of TBI with survival times between minutes and 7 days and 5 control cases with cardiovascular failure as the cause of death to determine acute changes in microglial morphology and antigen expression after TBI. In this pilot study, we detected highly localized changes in microglial morphology already early after traumatic damage, e.g., activated microglia and phagocyted erythrocytes in the contusion areas in cases with minute survival. Furthermore, an altered antigen expression was observed with increasing trauma wound age, showing similar effects like earlier transcriptomic studies. There is minute data on the direct impact of shear forces on microglial morphology. We were able to show localization-depending effects on microglial morphology causing localized dystrophy and adjacent activation. While rodent studies are widespread, they fail to mimic the exact mechanisms in human TBI response. Therefore, more studies focusing on cadaveric samples need to follow to thoroughly define the mechanisms leading to cell destruction and eventually evaluate their forensic value.

• Chronic traumatic encephalopathy
• Immunohistochemistry
• Inflammation
• Microglia
• Traumatic brain injury

• metastasis
• tumour invasion
• tumour microenvironment

• Cell Polarity/physiology
• Computational Biology/methods
• Cytokines/metabolism
• Humans
• Macrophage Activation/physiology
• Macrophages/metabolism
• Macrophages/physiology
• Phenotype
• Signal Transduction/physiology

• R01 HL141325 NHLBI NIH HHS
• F32 CA210482 NCI NIH HHS
• U01 CA212007 NCI NIH HHS
• R01 HL101200 NHLBI NIH HHS
• R01 CA138264 NCI NIH HHS
• National Institutes of Health
• American Heart Association

• immune cell
• inflammation
• ischemic stroke
• macrophage
• microglia

• annexin A2
• apoptosis
• autophagy
• human retinal endothelial cells
• oxygen-glucose deprivation

The sharing of molecules function that affects both tumor growth and neoangiogenesis with cells of the immune system creates a mutual interplay that impairs the host’s immune response against tumor progression. Increasing evidence shows that tumors are able to create an immunosuppressive microenvironment by recruiting specific immune cells. Moreover, molecules produced by tumor and inflammatory cells in the tumor microenvironment create an immunosuppressive milieu able to inhibit the development of an efficient immune response against cancer cells and thus fostering tumor growth and progression. In addition, the immunoediting could select cancer cells that are less immunogenic or more resistant to lysis. In this review, we summarize recent findings regarding the immunomodulatory effects and cancer progression of the angiogenic growth factor namely placental growth factor (PlGF) and address the biological complex effects of this cytokine. Different pathways of the innate and adaptive immune response in which, directly or indirectly, PlGF is involved in promoting tumor immune escape and metastasis will be described. PlGF is important for building up vascular structures and functions. Although PlGF effects on vascular and tumor growth have been widely summarized, its functions in modulating the immune intra-tumoral microenvironment have been less highlighted. In agreement with PlGF functions, different antitumor strategies can be envisioned.

• PlGF
• VEGF
• VEGFR
• cancer progression

• Angiogenesis Inducing Agents/metabolism
• Animals
• Disease Progression
• Drug Evaluation, Preclinical
• Humans
• Immunologic Surveillance
• Immunomodulation
• Molecular Targeted Therapy
• Neoplasms/drug therapy
• Neoplasms/etiology
• Neoplasms/metabolism
• Neoplasms/pathology
• Neovascularization, Pathologic/genetics
• Neovascularization, Pathologic/immunology
• Neovascularization, Pathologic/metabolism
• Placenta Growth Factor/genetics
• Placenta Growth Factor/metabolism
• Receptors, Neuropeptide/metabolism
• Signal Transduction

In mammals, the iron masterswitch hepcidin efficiently controls iron recycling by the macrophage-liver axis but the exact interplay between macrophages and hepatocytes remains poorly understood. We here study hepcidin response during macrophage differentiation as well as the macrophage-hepatocyte crosstalk and its subsequent effects on hepatocyte hepcidin using an in vitro co-culture model that mimics the physiological liver microenvironment. We show that macrophage differentiation strongly induces hepcidin by 60-fold both in THP1 macrophages and primary isolated monocyte-derived macrophages. Removal of H₂O₂ by catalase or inhibition of NOX2 efficiently blocked hepcidin induction. After differentiation, macrophage hepcidin accounted for 10% of total hepatocyte hepcidin and did not respond to low oxygen levels. In contrast, co-culture of differentiated macrophages with Huh7 cells significantly induced hepatocyte hepcidin, which was further potentiated under low oxygen levels. Hepatocyte hepcidin was also upregulated when Huh7 cells were solely exposed to macrophage-conditioned hypoxic medium. A cytokine screen identified macrophage secreted IL-1β as major inducer of hepcidin in hepatocytes. In confirmation, treatment of Huh7 cells with the IL-1 receptor antagonist (anakinra) completely blunted macrophage-mediated hepcidin transcription in hepatocytes. Finally, detailed analysis of potentially involved signaling pathways points toward STAT3 and CEBPδ-mediated hepcidin induction independent of IL-6. In conclusion, our study demonstrates a strong NOX2-mediated hepcidin induction during macrophage differentiation. These differentiated macrophages are able to efficiently induce hepatocyte hepcidin mainly through secretion of IL-1β. Our data highlight a hitherto unrecognized role of macrophage-hepatocyte crosstalk for a joint and oxygen-dependent hepcidin production through STAT3 and CEBPδ.

•

Hepcidin is strongly induced during NOX2-mediated macrophage differentiation in a H₂O₂-dependent manner.

• Cytokines
• Hydrogen peroxide
• Hypoxia
• Iron metabolism/hepcidin
• NADPH oxidase
• STAT3

• gene expression
• immune system
• microgravity
• oxygen

Microglia are the first source of a neuroinflammatory cascade, which seems to be involved in every phase of stroke-related neuronal damage. Two weeks after transient middle cerebral artery occlusion (MCAO), vehicle-treated rats displayed higher numbers of total ionized calcium-binding adaptor molecule 1 (Iba-1)-positive cells, greater cell body areas of Iba-1-positive cells, and higher numbers of hypertrophic Iba-1-positive cells (with a cell body area over 80 μm²) in the ipsilateral ischemic brain regions including the frontal cortex, striatum, and parietal cortex. In addition, MCAO decreased the number of migrating neuroblasts (or DCX- and 5-ethynyl-2′-deoxyuridine-positive cells) in the cortex, subventricular zone, and hippocampus of the ischemic brain, followed by neurological injury (including brain infarct and neurological deficits). Intravenous administration of human umbilical cord–derived mesenchymal stem cells (hUC-MSCs; 1 × 10⁶ or 4 × 10⁶) at 24 h after MCAO reduced neurological injury, decreased the number of hypertrophic microglia/macrophages, and increased the number of newborn neurons in rat brains. Thus, the accumulation of hypertrophic microglia/macrophages seems to be detrimental to neurogenesis after stroke. Treatment with hUC-MSCs preserved adult newborn neurons and reduced functional impairment after transient cerebral ischemia by reducing the number of hypertrophic microglia/macrophages.

• cell therapy
• microglia
• stroke
• umbilical cord mesenchymal stem cells

In muscular dystrophy and old age, skeletal muscle repair is compromised leading to fibrosis and fatty tissue accumulation. Therefore, therapies that protect skeletal muscle or enhance repair would be valuable medical treatments. Hypoxia-inducible factors (HIFs) regulate gene transcription under conditions of low oxygen, and HIF target genes EPO and VEGF have been associated with muscle protection and repair. We tested the importance of HIF activation following skeletal muscle injury, in both a murine model and human volunteers, using prolyl hydroxylase inhibitors that stabilize and activate HIF.

Using a mouse eccentric limb injury model, we characterized the protective effects of prolyl hydroxylase inhibitor, GSK1120360A. We then extended these studies to examine the impact of EPO modulation and infiltrating immune cell populations on muscle protection. Finally, we extended this study with an experimental medicine approach using eccentric arm exercise in untrained volunteers to measure the muscle-protective effects of a clinical prolyl hydroxylase inhibitor, daprodustat.

GSK1120360A dramatically prevented functional deficits and histological damage, while accelerating recovery after eccentric limb injury in mice. Surprisingly, this effect was independent of EPO, but required myeloid HIF1α-mediated iNOS activity. Treatment of healthy human volunteers with high-dose daprodustat reduced accumulation of circulating damage markers following eccentric arm exercise, although we did not observe any diminution of functional deficits with compound treatment.

The results of these experiments highlight a novel skeletal muscle protective effect of prolyl hydroxylase inhibition via HIF-mediated expression of iNOS in macrophages. Partial recapitulation of these findings in healthy volunteers suggests elements of consistent pharmacology compared to responses in mice although there are clear differences between these two systems.

The online version of this article (10.1186/s13395-018-0179-5) contains supplementary material, which is available to authorized users.

• Eccentric injury
• HIF activation
• Prolyl hydroxylase
• Protection
• Skeletal muscle

• Animal models
• Hypoxia
• Tissue remodelling
• Venous thrombosis

• Hypoxia/reoxygenation
• Macrophage
• Nicotinamide adenine dinucleotide phosphate oxidase 2
• Reactive oxygen species

• aging
• hypoxia
• mucosal tissues
• non-human primates
• periodontitis

Increasing evidence suggests a role for macrophages in the pathogenesis of age-related macular degeneration (AMD). This study examined choroidal macrophages and their activation in postmortem eyes from subjects with and without AMD.

Choroids were incubated with anti-ionized calcium-binding adapter molecule 1 (anti-IBA1) to label macrophages, anti-human leukocyte antigen-antigen D-related (anti-HLA-DR) as a macrophage activation marker, and Ulex europaeus agglutinin lectin to label blood vessels. Whole mounts were imaged using confocal microscopy. IBA1- and HLA-DR–positive (activated) cells were counted in submacula, paramacula, and nonmacula, and cell volume and sphericity were determined using computer-assisted image analysis.

In aged control eyes, the mean number of submacular IBA1⁺ and HLA-DR⁺ macrophages was 433/mm² and 152/mm², respectively. In early AMD eyes, there was a significant increase in IBA1⁺ and HLA-DR⁺ cells in submacula compared to those in controls (P = 0.0015 and P = 0.008, respectively). In eyes with neovascular AMD, there were significantly more HLA-DR⁺ cells associated with submacular choroidal neovascularization (P = 0.001). Mean cell volume was significantly lower (P ≤ 0.02), and sphericity was significantly higher (P ≤ 0.005) in all AMD groups compared to controls.

The average number of IBA1⁺ macrophages in submacular and paramacular choroid was significantly higher in early/intermediate AMD compared to that in aged controls. HLA-DR⁺ submacular macrophages were significantly increased in all stages of AMD, and they were significantly more round and smaller in size in the submacular AMD choroid, suggesting their activation. These findings support the concept that AMD is an inflammatory disease.

Macrophages are known to interact with endothelial cells during developmental and pathological angiogenesis but the molecular mechanisms modulating these interactions remain unclear. Here, we show a role for the Hif-1α transcription factor in this cellular communication. We generated hif-1aa;hif-1ab double mutants in zebrafish, hereafter referred to as hif-1α mutants, and find that they exhibit impaired macrophage mobilization from the aorta-gonad-mesonephros (AGM) region as well as angiogenic defects and defective vascular repair. Importantly, macrophage ablation is sufficient to recapitulate the vascular phenotypes observed in hif-1α mutants, revealing for the first time a macrophage-dependent angiogenic process during development. Further substantiating our observations of vascular repair, we find that most macrophages closely associated with ruptured blood vessels are Tnfα-positive, a key feature of classically activated macrophages. Altogether, our data provide genetic evidence that Hif-1α regulates interactions between macrophages and endothelial cells starting with the mobilization of macrophages from the AGM.

The molecular mechanism regulating macrophage interaction with endothelial cells during development is unclear. Here, the authors show that in zebrafish mutation of hypoxia-inducible factor-1α impairs macrophage mobilization from the aorta-gonad-mesonephros, causing defects in angiogenesis and vessel repair.

• CD39; CD73
• adaptive immunity
• blood–brain barrier
• brain ischemia
• inflammation
• innate immunity

One of the hallmarks of cancer-related inflammation is the recruitment of monocyte-macrophage lineage cells to the tumor microenvironment. These tumor infiltrating myeloid cells are educated by the tumor milieu, rich in cancer cells and stroma components, to exert functions such as promotion of tumor growth, immunosuppression, angiogenesis, and cancer cell dissemination. Our review highlights the ontogenetic diversity of tumor-associated macrophages (TAMs) and describes their main phenotypic markers. We cover fundamental molecular players in the tumor microenvironment including extra- (CCL2, CSF-1, CXCL12, IL-4, IL-13, semaphorins, WNT5A, and WNT7B) and intracellular signals. We discuss how these factors converge on intracellular determinants (STAT3, STAT6, STAT1, NF-κB, RORC1, and HIF-1α) of cell functions and drive the recruitment and polarization of TAMs. Since microRNAs (miRNAs) modulate macrophage polarization key miRNAs (miR-146a, miR-155, miR-125a, miR-511, and miR-223) are also discussed in the context of the inflammatory myeloid tumor compartment. Accumulating evidence suggests that high TAM infiltration correlates with disease progression and overall poor survival of cancer patients. Identification of molecular targets to develop new therapeutic interventions targeting these harmful tumor infiltrating myeloid cells is emerging nowadays.

• 3T3-L1 Cells
• Adipose Tissue/metabolism
• Angiopoietin-1/metabolism
• Animals
• Cells, Cultured
• Diet, High-Fat/adverse effects
• Female
• Fibroblast Growth Factor 1/metabolism
• Fibroblast Growth Factor 10/metabolism
• Glucose Tolerance Test
• Hypoxia-Inducible Factor 1, alpha Subunit/genetics
• Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
• Inflammation/etiology
• Inflammation/metabolism
• Insulin Resistance/genetics
• Macrophages/metabolism
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Myeloid Cells/metabolism
• Neovascularization, Pathologic/etiology
• Neovascularization, Pathologic/metabolism
• Vascular Endothelial Growth Factor A/metabolism

Since the observation of Virchow, it has long been known that the tumor microenvironment constitutes the soil for the infiltration of inflammatory cells and for the release of inflammatory mediators. Under certain circumstances, inflammation remains unresolved and promotes cancer development. Here, we review some of these indisputable experimental and clinical evidences of cancer related smouldering inflammation. The most common myeloid infiltrate in solid tumors is composed of myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs). These cells promote tumor growth by several mechanisms, including their inherent immunosuppressive activity, promotion of neoangiogenesis, mediation of epithelial-mesenchymal transition and alteration of cellular metabolism. The pro-tumoral functions of TAMs and MDSCs are further enhanced by their cross-talk offering a myriad of potential anti-cancer therapeutic targets. We highlight these main pro-tumoral mechanisms of myeloid cells and give a general overview of their phenotypical and functional diversity, offering examples of possible therapeutic targets. Pharmacological targeting of inflammatory cells and molecular mediators may result in therapies improving patient condition and prognosis. Here, we review experimental and clinical findings on cancer-related inflammation with a major focus on creating an inventory of current small molecule-based therapeutic interventions targeting cancer-related inflammatory cells: TAMs and MDSCs.

• inflammatory tumor microenvironment
• myeloid-derived suppressor cells
• tumor-associated macrophages

• Antineoplastic Agents/therapeutic use
• Cell Communication/drug effects
• Cell Movement/drug effects
• Cytokines/genetics
• Cytokines/immunology
• Epithelial-Mesenchymal Transition/drug effects
• Gene Expression Regulation, Neoplastic
• Humans
• Inflammation/prevention & control
• Macrophages/drug effects
• Macrophages/immunology
• Macrophages/pathology
• Molecular Targeted Therapy
• Myeloid-Derived Suppressor Cells/drug effects
• Myeloid-Derived Suppressor Cells/immunology
• Myeloid-Derived Suppressor Cells/pathology
• Neoplasm Proteins/genetics
• Neoplasm Proteins/immunology
• Neoplasms/drug therapy
• Neoplasms/genetics
• Neoplasms/immunology
• Neoplasms/pathology
• Neovascularization, Pathologic/drug therapy
• Neovascularization, Pathologic/genetics
• Neovascularization, Pathologic/immunology
• Neovascularization, Pathologic/pathology
• Small Molecule Libraries/therapeutic use
• Tumor Microenvironment/drug effects
• Tumor Microenvironment/genetics
• Tumor Microenvironment/immunology

• cancer
• hypoxia
• inflammation
• macrophage
• tumor microenvironment

• angiogenesis
• chronic inflammation
• endothelium
• vascular remodeling
• vasculogenesis

• Microglia/macrophage
• Morphology
• Neurogenesis
• Polarization
• Stroke
• Therapy

• Activation
• Epigenetic
• Gene expression
• Macrophage
• Metabolism
• Plasticity

• Angiogenesis
• Anticancer therapy
• Apoptosis
• Burkitt lymphoma
• Cell death
• Extracellular vesicle
• Macrophage
• Onco-regenerative niche
• Starry-sky
• Tumor microenvironment