Nonresolving macrophage‐mediated inflammation in malignancy

Murray, Peter J.

doi:10.1111/febs.14210

Cited by 35 publications

(42 citation statements)

References 107 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For the most part, the intrinsic variabilities of macrophages from different locations are unfortunately ignored in the current system of macrophage categorization. In TAMs, the expression of genes normally associated with M2 macrophages, such Arg1 , Mrc1 and others, led to the likening of these two macrophage populations (Murray, 2018). This idea was further supported by the anti-inflammatory role that TAMs can acquire in tumors, where they have been shown to secrete pro-tumoral signals (Kitamura et al, 2015; Quail et al, 2016), recruit other anti-inflammatory cells (Curiel et al, 2004), de-differentiate into and from myeloid-derived suppressor cells (MDSCs; Box 1) (Corzo et al, 2010), and dampen the T cell response (Dong et al, 2002; Gallina et al, 2006; Rodriguez et al, 2004).…”

Section: The Inflammatory Axis Of Macrophage Polarizationmentioning

confidence: 99%

“…This idea was further supported by the anti-inflammatory role that TAMs can acquire in tumors, where they have been shown to secrete pro-tumoral signals (Kitamura et al, 2015; Quail et al, 2016), recruit other anti-inflammatory cells (Curiel et al, 2004), de-differentiate into and from myeloid-derived suppressor cells (MDSCs; Box 1) (Corzo et al, 2010), and dampen the T cell response (Dong et al, 2002; Gallina et al, 2006; Rodriguez et al, 2004). As with TAMs, M2-like macrophages favor tumor growth (see, for example, Hughes et al, 2015; Lujambio et al, 2013; Murray, 2018). Consistently, the repolarization of TAMs into phenotypes that more closely resemble M1 macrophages has successfully produced anti-tumoral responses in pre-clinical murine models (Hughes et al, 2015; Mantovani et al, 2017; Pyonteck et al, 2013).…”

Section: The Inflammatory Axis Of Macrophage Polarizationmentioning

confidence: 99%

See 1 more Smart Citation

The metabolic axis of macrophage and immune cell polarization

Hobson-Gutierrez

Carmona‐Fontaine

2018

Disease Models &Amp; Mechanisms

View full text Add to dashboard Cite

The extracellular space of solid tumors ranges from being well-nurtured to being completely ischemic and can serve as a source of intratumoral heterogeneity, determining the behavior and molecular profiles of malignant and stromal cells. Here, we discuss how the metabolic tumor microenvironment modulates the phenotypes of the immune cells that infiltrate tumors, with an emphasis on tumor-associated macrophages. These cells constitute a diverse population that has pro-tumoral and anti-inflammatory properties, and are likened to anti-inflammatory ‘M2’ macrophages. Recent findings show how different metabolic microenvironments specify an array of phenotypic changes in macrophages. In tumors, extracellular metabolite levels vary predictably according to proximity to the vasculature, and phenotypic changes in tumor-associated macrophages and in other immune cells are also predictable. We speculate that this ‘metabolic axis’ of macrophage polarization modulates – and is modulated by – the response to inflammatory cues, creating a wide variety of possible phenotypic states. Understanding how extracellular metabolites influence cell phenotypes allows us to predict how tumor-associated macrophages and other tumor cells might change, with the aim of harnessing this predictability for therapy. Overall, we describe an emerging picture in which chemokines, growth factors and the metabolic tumor microenvironment act together to determine the phenotypes of tumor-infiltrating immune cells.

show abstract

Section: The Inflammatory Axis Of Macrophage Polarizationmentioning

confidence: 99%

Section: The Inflammatory Axis Of Macrophage Polarizationmentioning

confidence: 99%

The metabolic axis of macrophage and immune cell polarization

Hobson-Gutierrez

Carmona‐Fontaine

2018

Disease Models &Amp; Mechanisms

View full text Add to dashboard Cite

show abstract

“…

…”

mentioning

confidence: 99%

Cxcr3-expressing leukocytes are necessary for neurofibroma formation in mice

Fletcher

Jessen

et al. 2019

JCI Insight

View full text Add to dashboard Cite

macrophage subpopulations with distinct activities (24,25). Further characterization of these neurofibroma leukocytes and their contributions to tumor initiation and growth is necessary for the development of safe and effective immunomodulatory therapies.In the Dhh-Cre Nf1 fl/fl mouse neurofibroma model, biallelic deletion of Nf1 in the Schwann cell lineage mimics the biallelic loss of NF1 in human NF1 and sporadic plexiform neurofibroma (26). The peripheral nerves of these mice appear normal at 1 month of age, but pathological changes, including mast cell and macrophage infiltration and abnormal Schwann cell proliferation, are evident at 2 months of age (26,27). By 4 months of age, these mice invariably form MRI-detectable paraspinal neurofibromas that histologically and transcriptionally resemble human plexiform neurofibroma (26,28,29). Schwann cell-specific deletion of Nf1 using other drivers can also induce nerve pathology and neurofibroma development in mice (19,(30)(31)(32). In contrast, CNPase-human EGFR (CNPase-hEGFR) mice have increased Ras activity driven by overexpression of hEGFR and develop similar nerve pathology to Nf1 mouse models but have reduced myeloid cell infiltration, and only approximately 1 in 20 develop a neurofibroma (20,33).Here, we compare nerves from these mouse models transcriptionally and identify a chemokine, Cxcl10, that is uniquely overexpressed in 2-month Dhh-Cre Nf1 fl/fl nerves. CXCL10 and its receptor, CXCR3, are important modulators of neuroinflammation and tumor biology (34)(35)(36). In this study, we identify Cxcl10and Cxcr3-expressing cell populations in nerves and neurofibroma and demonstrate the necessity of Cxcr3 for neurofibroma development in Dhh-Cre Nf1 fl/fl mice. Results Differential gene expression analyses identify Cxcl10 as a potential modulator of plexiform neurofibroma development.Peripheral nerves from GEMMs of NF1 (GEMM-NF1) (P0-CreB Nf1 fl/fl , P0-CreB Nf1 fl/-, Dhh-Cre Nf1 fl/fl ) invariably develop neurofibromas (26,31). P0-CreB and Dhh-Cre are transgenic mouse strains that express Cre recombinase in peripheral nerve Schwann cells; when used to recombine Nf1 in mice, peripheral nerves show pathological mast cell recruitment, disruption of axon and nonmyelinating Schwann cell (axon/ Remak bundle) interactions, and collagen deposition (nerve disruption). This nerve disruption phenotype precedes plexiform neurofibroma development. Although several of these changes have been proposed to contribute to neurofibroma development, similar nerve pathology is also observed in CNPase-hEGFR/ + and CNPase-hEGFR/CNPase-hEGFR mice, which recruit fewer macrophages and rarely form neurofibromas (33,37). In contrast, this pathology is not observed in Npcis mice (Nf1 +/− Trp53 +/− deletions in cis) that progress directly to malignant peripheral nerve sheath tumor (ref. 38 and Supplemental Figure 1; supplemental material available online with this article; https://doi.org/10.1172/jci.insight.98601DS1) or in CNPase-HRas12V mice that do not develop plexiform neurofibroma (39)....

show abstract

“…Peter Murray focuses on the factors and signaling pathways that promote the protumor activities of tumor‐associated macrophages . His review also describes the present limitations of any therapy aimed at depleting macrophages from tumors . Pascale Jeannin et al .…”

mentioning

confidence: 99%

“…Peter Murray focuses on the factors and signaling pathways that promote the protumor activities of tumor-associated macrophages [12]. His review also describes the present limitations of any therapy aimed at depleting macrophages from tumors [12]. Pascale Jeannin et al [13] review the signals that regulate functional plasticity in macrophages, while focusing on three key differentiation factors: Macrophage colony-stimulating factor (M-CSF), Interleukin 34 (IL-34) and Granulocyte M-CSF (GM-CSF) and their roles within the TME.…”

mentioning

confidence: 99%