Targeting Macrophages as a Potential Therapeutic Intervention: Impact on Inflammatory Diseases and Cancer.

Published on Jul 4, 2018in International Journal of Molecular Sciences4.556
· DOI :10.3390/IJMS19071953
Mirco Ponzoni55
Estimated H-index: 55
(Istituto Giannina Gaslini),
Fabio Pastorino34
Estimated H-index: 34
(Istituto Giannina Gaslini)
+ 2 AuthorsChiara Brignole29
Estimated H-index: 29
(Istituto Giannina Gaslini)
Sources
Abstract
Macrophages, cells belonging to the innate immune system, present a high plasticity grade, being able to change their phenotype in response to environmental stimuli. They play central roles during development, homeostatic tissue processes, tissue repair, and immunity. Furthermore, it is recognized that macrophages are involved in chronic inflammation and that they play central roles in inflammatory diseases and cancer. Due to their large involvement in the pathogenesis of several types of human diseases, macrophages are considered to be relevant therapeutic targets. Nanotechnology-based systems have attracted a lot of attention in this field, gaining a pivotal role as useful moieties to target macrophages in diseased tissues. Among the different approaches that can target macrophages, the most radical is represented by their depletion, commonly obtained by means of clodronate-containing liposomal formulations and/or depleting antibodies. These strategies have produced encouraging results in experimental mouse models. In this review, we focus on macrophage targeting, based on the results so far obtained in preclinical models of inflammatory diseases and cancer. Pros and cons of these therapeutic interventions will be highlighted.
Download
📖 Papers frequently viewed together
427 Citations
7 Citations
41 Citations
References96
Newest
#1Fernando Torres Andón (University of Santiago de Compostela)H-Index: 13
#2Elisabeth Digifico (Humanitas University)H-Index: 3
Last. Paola AllavenaH-Index: 90
view all 7 authors...
Abstract The engineering of new nanomedicines with ability to target and kill or re-educate Tumor Associated Macrophages (TAMs) stands up as a promising strategy to induce the effective switching of the tumor-promoting immune suppressive microenvironment, characteristic of tumors rich in macrophages, to one that kills tumor cells, is anti-angiogenic and promotes adaptive immune responses. Alternatively, the loading of monocytes/macrophages in blood circulation with nanomedicines, may be used to ...
56 CitationsSource
#1Shweta Aras (TU: Temple University)H-Index: 7
#2M. Raza Zaidi (TU: Temple University)H-Index: 17
Macrophages are conventionally classified into M1 and M2 subtypes according to their differentiation status and functional role in the immune system. However, accumulating evidence suggests that this binary classification system is insufficient to account for the remarkable plasticity of macrophages that gives rise to an immense diversity of subtypes. This diverse spectrum of macrophage subtypes play critical roles in various homeostatic and immune functions, but remain far from being fully char...
254 CitationsSource
#1Xia Yuan (Sichuan University)H-Index: 2
#2Jing Zhang (Sichuan University)H-Index: 1
Last. Xuelei Ma (Sichuan University)H-Index: 26
view all 7 authors...
Abstract Objective The role of tumor-associated macrophages (TAMs) in tumor microenvironment remains controversial due to the two different polarized subsets of TAMs. Here, we performed a meta-analysis to evaluate the correlation between subpopulations of TAMs and clinical outcomes in patients with ovarian cancer. Methods A comprehensive search in PUBMED/Medline and EMBASE databases was performed. The association between TAMs and patient prognosis of ovarian cancer was estimated with hazard rati...
89 CitationsSource
#2Larry Gluck (Greenville Health System)H-Index: 2
Last. Joe Stephenson (Greenville Health System)H-Index: 8
view all 11 authors...
Purpose: Binding of colony-stimulating factor 1 (CSF1) ligand to the CSF1 receptor (CSF1R) regulates survival of tumor-associated macrophages, which generally promote an immunosuppressive tumor microenvironment. AMG 820 is an investigational, fully human CSF1R antibody that inhibits binding of the ligands CSF1 and IL34 and subsequent ligand-mediated receptor activation. This first-in-human phase I study evaluated the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of AMG 820. ...
70 CitationsSource
#1Monica Falleni (University of Milan)H-Index: 22
#2Federica SaviH-Index: 12
Last. Gaetano BulfamanteH-Index: 31
view all 7 authors...
Skin malignant melanoma (MM) is an aggressive cancer with an increasing incidence with limited therapies in advanced stages. Tumor-associated macrophages (TAMs) are the major immune constituent of the MM microenvironment and contribute toward its prognosis. TAMs’ characterization and localization in human cancer is important to understand cancer progression and to identify molecular personalized therapies. M2 TAMs in stage I–II MMs are associated with worse prognostic parameters. A comprehensive...
39 CitationsSource
#1Yuvraj Singh (Central Drug Research Institute)H-Index: 14
#2Vivek K. Pawar (Central Drug Research Institute)H-Index: 16
Last. Manish K. Chourasia (Central Drug Research Institute)H-Index: 25
view all 8 authors...
Abstract Recruitment of inflammatory cells to tumor has been well documented, with the most frequent inhabitants being macrophages termed as tumor associated macrophages, (TAMs). Their presence was thought to be an evidence of immune system initiating a fight response towards the tumor, i.e. immune surveillance. This is the case too initially, when TAMs majorly exhibit an M1 phenotype, but their continued presence in tumor microenvironment brings about their polarization to M2 phenotype, which n...
47 CitationsSource
#1Xixi Zhao (Xi'an Jiaotong University)H-Index: 4
#2Jingkun Qu (Xi'an Jiaotong University)H-Index: 8
Last. Shuqun ZhangH-Index: 15
view all 11 authors...
// Xixi Zhao 1,* , Jingkun Qu 2,* , Yuchen Sun 3 , Jizhao Wang 2 , Xu Liu 2 , Feidi Wang 1 , Hong Zhang 1 , Wen Wang 1 , Xingcong Ma 1 , Xiaoyan Gao 1 and Shuqun Zhang 1 1 Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, P.R. China 2 The Second Department of Thoracic Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, P.R. China 3 The Department of Radiation Oncology, The First Affiliated Hospital of Xi'an Jiao ...
130 CitationsSource
#1Alberto MantovaniH-Index: 200
#2Federica Marchesi (University of Milan)H-Index: 31
Last. P. Allavena (Humanitas University)H-Index: 20
view all 5 authors...
Tumour-associated macrophages (TAMs) are key drivers of tumour-promoting inflammation and cancer progression, and are important determinants of responsiveness to a range of therapies. Herein, the authors summarize the roles of TAMs in cancer, and discuss the potential of TAM-targeted therapeutic strategies to complement and synergize with other anticancer treatments.
1,254 CitationsSource
#1Xu Wang (Soochow University (Suzhou))H-Index: 9
#1X.L. Wang (Soochow University (Taiwan))H-Index: 1
Last. C.P. WuH-Index: 1
view all 3 authors...
Tumor-associated macrophages (TAMs), which play a crucial role in the tumor microenvironment, can be divided into M1 and M2 phenotypes, these phenotypes may exert opposite effects on the prognoses of patients with gastric cancer (GC). The association between TAMs and GC is contentious. Thus, a meta-analysis of 12 studies (incorporating 1388 patients) retrieved from the Cochrane Library, PubMed, and Embase databases was conducted in order to evaluate the relationship between TAMs and GC prognosis...
24 CitationsSource
#1Saeid Zanganeh (Stanford University)H-Index: 21
#2Gregor Hutter (Stanford University)H-Index: 17
Last. Heike E. Daldrup-Link (Stanford University)H-Index: 52
view all 12 authors...
The Food and Drug Administration (FDA)-approved iron supplement ferumoxytol, which contains iron oxide nanoparticles, can suppress growth of early mammary cancers and lung cancer metastasis by inducing pro-inflammatory M1 type macrophage polarization in the tumour tissue, offering a new ‘off label’ application for an approved drug.
601 CitationsSource
Cited By53
Newest
#1Yuejia Song (CSU: Central South University)
#2Yaqian Huang (CSU: Central South University)
Last. Wenhu Zhou (CSU: Central South University)
view all 5 authors...
Abstract null null Macrophage is the key innate immune effector in first-line defense against the pathogens, and can be polarized into different phenotypes to regulate a variety of immunological functions. However, the plasticity of macrophage is extraordinarily recruited, activated, and polarized under pathological conditions, playing paramount roles in occurrence, development, and prognosis of various chronic diseases, such as rheumatoid arthritis (RA), atherosclerosis (AS), and cancer. To thi...
Source
#1Nadim Ahamad (IITB: Indian Institute of Technology Bombay)H-Index: 4
#2Abhinanda Kar (IITB: Indian Institute of Technology Bombay)
Last. Rinti Banerjee (IITB: Indian Institute of Technology Bombay)H-Index: 32
view all 8 authors...
Abstract Inflammatory disease (ID) is an umbrella term encompassing all illnesses involving chronic inflammation as the central manifestation of pathogenesis. These include, inflammatory bowel diseases, hepatitis, pulmonary disorders, atherosclerosis, myocardial infarction, pancreatitis, arthritis, periodontitis, psoriasis. The IDs create a severe burden on healthcare and significantly impact the global socio-economic balance. Unfortunately, the standard therapies that rely on a combination of a...
Source
#1Tobias A. Bauer (LEI: Leiden University)H-Index: 1
#2Natalie K Horvat (Heidelberg University)
Last. Kaloian Koynov (MPG: Max Planck Society)H-Index: 51
view all 17 authors...
Iron is an essential co-factor for cellular processes. In the immune system, it can activate macrophages and represents a potential therapeutic for various diseases. To specifically deliver iron to macrophages, iron oxide nanoparticles are embedded in polymeric micelles of reactive polysarcosine-block-poly(S-ethylsulfonyl-l-cysteine). Upon surface functionalization via dihydrolipoic acid, iron oxide cores act as crosslinker themselves and undergo chemoselective disulfide bond formation with the ...
Source
Macrophages are a specialized class of innate immune cells with multifaceted roles in modulation of the inflammatory response, homeostasis, and wound healing. While developmentally derived or originating from circulating monocytes, naive macrophages can adopt a spectrum of context-dependent activation states ranging from pro-inflammatory (classically activated, M1) to pro-wound healing (alternatively activated, M2). Tumors are known to exploit macrophage polarization states to foster a tumor-per...
1 CitationsSource
Macrophages were discovered in the 19th century by Ukrainian biologist Elie Metchnikoff who worked in Ukraine, Russia, and France [...].
Source
Targeting the innate immune system has attracted attention with the development of anti- CD47 antibodies. Anti-CD47 antibodies block the inhibition of the phagocytic activity of macrophages caused by the up-regulation of CD47 on tumor cells. In this study, public genomic data was used to identify genes highly expressed in breast tumors with elevated CD47 expression and analyzed the association between the presence of tumor immune infiltrates and the expression of the selected genes. We found tha...
Source
#1Linlin Yang (UNC: University of North Carolina at Chapel Hill)
#2Alison M. Rojas (UNC: University of North Carolina at Chapel Hill)
Last. Celia E. Shiau (UNC: University of North Carolina at Chapel Hill)
view all 3 authors...
The ability to conduct in vivo macrophage-specific depletion remains an effective means to uncover functions of macrophages in a wide range of physiological contexts. Compared to the murine model, zebrafish offer superior imaging capabilities due to their optical transparency starting from a single-cell stage to throughout larval development. These qualities become important for in vivo cell specific depletions so that the elimination of the targeted cells can be tracked and validated in real ti...
Source
#1Juan G. ValeroH-Index: 8
#2Alba Matas-Céspedes (AstraZeneca)H-Index: 7
Last. Patricia Pérez-GalánH-Index: 16
view all 20 authors...
Microenvironment contributes to follicular lymphoma (FL) pathogenesis and impacts survival with macrophages playing a controversial role. In the present study, using FL primary samples and HK follicular dendritic cells (FDC) to mimic the germinal center, together with mouse models, we have analyzed the three-way crosstalk of FL-FDC-macrophages and derived therapeutic opportunities. Ex vivo primary FL-FDC co-cultures (n = 19) and in vivo mouse co-xenografts demonstrated that FL-FDC crosstalk favo...
2 CitationsSource
#1Sylwia Cyboran-Mikołajczyk (Wroclaw University of Environmental and Life Sciences)H-Index: 3
Last. Magdalena Wawrzyńska (Wrocław Medical University)H-Index: 9
view all 10 authors...
Liposomal technologies are used in order to improve the effectiveness of current therapies or to reduce their negative side effects. However, the liposome–erythrocyte interaction during the intravenous administration of liposomal drug formulations may result in changes within the red blood cells (RBCs). In this study, it was shown that phosphatidylcholine-composed liposomal formulations of Photolon, used as a drug model, significantly influences the transmembrane potential, stiffness, as well as...
Source
#1Guangan Hu (MIT: Massachusetts Institute of Technology)H-Index: 10
#2Yang Su (MIT: Massachusetts Institute of Technology)H-Index: 1
Last. Jianzhu Chen (MIT: Massachusetts Institute of Technology)H-Index: 77
view all 9 authors...
Macrophages are plastic and, in response to different local stimuli, can polarize toward multi-dimensional spectrum of phenotypes, including the pro-inflammatory M1-like and the anti-inflammatory M2-like states. Using a high-throughput phenotypic screen in a library of ~4000 FDA-approved drugs, bioactive compounds and natural products, we find ~300 compounds that potently activate primary human macrophages toward either M1-like or M2-like state, of which ~30 are capable of reprogramming M1-like ...
2 CitationsSource