Class A1 scavenger receptor modulates glioma progression by regulating M2-like tumor-associated macrophage polarization

Zhang, Hanwen; Zhang, Wenbin; Sun, Xuan; Dang, Rui; Zhou, Rong‐Mei; Bai, Hui; Ben, Jingjing; Zhu, Xudong; Zhang, Yan; Yang, Qing; Xu, Yong; Chen, Qi

doi:10.18632/oncotarget.10318

Cited by 30 publications

(16 citation statements)

References 57 publications

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“…While it is well documented that GAMs have an M2-like phenotype ( 37 , 38 , 46 , 47 ), the majority of data did not compare tumors longitudinally to understand whether GAMs begin as M2-like or whether there is a phenotypic shift. Our longitudinal clinical data confirm that GAMs assume a classically activate M1 phenotype early on in tumor growth and as the tumor progresses to a more advanced stage, these GAMs switch to resemble an alternatively activated M2 phenotype ( 48 , 49 ). This has now been shown to be related to the level of hypoxia within the tumors ( 50 – 52 ).…”

Section: Discussionsupporting

confidence: 65%

Glioblastoma Recurrence Correlates With Increased APE1 and Polarization Toward an Immuno-Suppressive Microenvironment

et al. 2018

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While treatment with surgery, radiotherapy and/or chemotherapy may prolong life for patients with glioblastoma, recurrence is inevitable. What is still being discovered is how much these treatments and recurrence of disease affect the molecular profiles of these tumors and how these tumors adapt to withstand these treatment pressures. Understanding such changes will uncover pathways used by the tumor to evade destruction and will elucidate new targets for treatment development. Nineteen matched pre-treatment and post-treatment glioblastoma tumors were subjected to gene expression profiling (Fluidigm, TaqMan assays), MGMT promoter methylation analysis (pyrosequencing) and protein expression analysis of the DNA repair pathways, known to be involved in temozolomide resistance (immunohistochemistry). Gene expression profiling to molecularly subtype tumors revealed that 26% of recurrent post-treatment specimens did not match their primary diagnostic specimen subtype. Post-treatment specimens had molecular changes which correlated with known resistance mechanisms including increased expression of APEX1 (p < 0.05) and altered MGMT methylation status. In addition, genes associated with immune suppression, invasion and aggression (GPNMB, CCL5, and KLRC1) and polarization toward an M2 phenotype (CD163 and MSR1) were up-regulated in post-treatment tumors, demonstrating an overall change in the tumor microenvironment favoring aggressive tumor growth and disease recurrence. This was confirmed by in vitro studies that determined that glioma cell migration was enhanced in the presence of M2 polarized macrophage conditioned media. Further, M2 macrophage-modulated migration was markedly enhanced in post-treatment (temozolomide resistant) glioma cells. These findings highlight the ability of glioblastomas to evade not only the toxic onslaught of therapy but also to evade the immune system suggesting that immune-altering therapies may be of value in treating this terrible disease.

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Section: Discussionsupporting

confidence: 65%

Glioblastoma Recurrence Correlates With Increased APE1 and Polarization Toward an Immuno-Suppressive Microenvironment

et al. 2018

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“…The proposed mechanisms of action involve interrupting TAM/cancer cell crosstalk, blocking SR-A1 from scavenging ECM components that allow for cancer cell migration, and scavenging of pro-inflammatory/angiogenic lysophosphatidic acid (LPA) [151]. However, in the context of glioma model, Zhang et al demonstrated that recognition of tumor-secreted heat shock protein 70 (HSP70) by SR-A1 is important in suppressing M2 polarization in TAMs and is needed for inhibition of glioma proliferation and angiogenesis [152]. These studies highlight the context-dependent effect in modulation of scavenger receptor activity as a result of its recognition of a broad range of ligands.…”

Section: Pharmacological Modulation Of Macrophages/tamsmentioning

confidence: 99%

Progress in tumor-associated macrophage (TAM)-targeted therapeutics

Ngambenjawong

Gustafson

Pun

2017

Advanced Drug Delivery Reviews

642

484

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As an essential innate immune population for maintaining body homeostasis and warding off foreign pathogens, macrophages display high plasticity and perform diverse supportive functions specialized to different tissue compartments. Consequently, aberrance in macrophage functions contributes substantially to progression of several diseases including cancer, fibrosis, and diabetes. In the context of cancer, tumor-associated macrophages (TAMs) in tumor microenvironment (TME) typically promote cancer cell proliferation, immunosuppression, and angiogenesis in support of tumor growth and metastasis. Oftentimes, the abundance of TAMs in tumor is correlated with poor disease prognosis. Hence, significant attention has been drawn towards development of cancer immunotherapies targeting these TAMs; either depleting them from tumor, blocking their pro-tumoral functions, or restoring their immunostimulatory/tumoricidal properties. This review aims to introduce readers to various aspects in development and evaluation of TAM-targeted therapeutics in pre-clinical and clinical stages.

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“…STAT3 activation in tumor-associated macrophages (TAMs) has also been associated with their acquirement of pro-tumorigenic features. In a rat model of breast cancer, STAT3 inhibition could revert a TAM immune suppressing phenotype leading to immune-mediated inhibition of tumor growth [133], and STAT3 was shown to promote pro-tumorigenic M2 polarization of TAMs in glioma, enhancing proliferation and angiogenesis [134]. This activity may be due to STAT3mediated expression of the B7-H4 T-cell co-inhibitory molecule that impairs CD8 + T cell activation [135].…”

Section: Tumor Associated Macrophages (Tams)mentioning

confidence: 99%

STAT3 in cancer: A double edged sword

et al. 2017

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The transcription factor signal transducer and activator of transcription (STAT) 3 is activated downstream of cytokines, growth factors and oncogenes to mediate their functions under both physiological and pathological conditions. In particular, aberrant/unrestrained STAT3 activity is detected in a wide variety of tumors, driving multiple pro-oncogenic functions. For that, STAT3 is widely considered as an oncogene and is the object of intense translational studies. One of the distinctive features of this factor is however, its ability to elicit different and sometimes contrasting effects under different conditions. In particular, STAT3 activities have been shown to be either pro-oncogenic or tumor-suppressive according to the tumor aetiology/mutational landscape, suggesting that the molecular bases underlining its functions are still incompletely understood. Here we discuss some of the properties that may provide the bases to explain STAT3 heterogeneous functions, and in particular how post-translational modifications contribute shaping its sub-cellular localization and activities, the cross talk between these activities and cell metabolic conditions, and finally how its functions can control the behaviour of both tumor and tumor microenvironment cell populations.

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Class A1 scavenger receptor modulates glioma progression by regulating M2-like tumor-associated macrophage polarization

Cited by 30 publications

References 57 publications

Glioblastoma Recurrence Correlates With Increased APE1 and Polarization Toward an Immuno-Suppressive Microenvironment

Glioblastoma Recurrence Correlates With Increased APE1 and Polarization Toward an Immuno-Suppressive Microenvironment

Progress in tumor-associated macrophage (TAM)-targeted therapeutics

STAT3 in cancer: A double edged sword

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