Distinct roles of <scp>CSF</scp> family cytokines in macrophage infiltration and activation in glioma progression and injury response

Sielska, Małgorzata; Przanowski, Piotr; Wylot, Bartosz; Gabrusiewicz, Konrad; Maleszewska, Marta; Kijewska, Magdalena; Zawadzka, Małgorzata; Kucharska, Joanna; Vinnakota, Katyayni; Kettenmann, Helmut; Kotulska, Katarzyna; Grajkowska, Wiesława; Kamińska, Bożena

doi:10.1002/path.4192

Cited by 132 publications

(126 citation statements)

References 56 publications

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“…The complexity of GM-CSF biology is evident, because it is implicated in inflammatory conditions, such as rheumatoid arthritis and crescentic GN, 33 but also, as an inducer of M2 markers in microglia/macrophages surrounding glioblastoma tumor cells. 34 Nonhematopoietic cells, such as vascular smooth muscle cells and colon epithelial cells, have been reported to be important sources of GM-CSF, mediating atherogenic monocyte activation 35 and promoting colonic epithelial cell proliferation in colitis, 36 respectively. In addition, GM-CSF has been associated to Th2 immune responses in allergic lung inflammation.…”

Section: Discussionmentioning

confidence: 99%

GM-CSF Promotes Macrophage Alternative Activation after Renal Ischemia/Reperfusion Injury

Huen¹,

Huynh

Marlier³

et al. 2015

Journal of the American Society of Nephrology

101

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After kidney ischemia/reperfusion (I/R) injury, monocytes home to the kidney and differentiate into activated macrophages. Whereas proinflammatory macrophages contribute to the initial kidney damage, an alternatively activated phenotype can promote normal renal repair. The microenvironment of the kidney during the repair phase mediates the transition of macrophage activation from a proinflammatory to a reparative phenotype. In this study, we show that macrophages isolated from murine kidneys during the tubular repair phase after I/R exhibit an alternative activation gene profile that differs from the canonical alternative activation induced by IL-4-stimulated STAT6 signaling. This unique activation profile can be reproduced in vitro by stimulation of bone marrow-derived macrophages with conditioned media from serum-starved mouse proximal tubule cells. Secreted tubular factors were found to activate macrophage STAT3 and STAT5 but not STAT6, leading to induction of the unique alternative activation pattern. Using STAT3-deficient bone marrow-derived macrophages and pharmacologic inhibition of STAT5, we found that tubular cell-mediated macrophage alternative activation is regulated by STAT5 activation. Both in vitro and after renal I/R, tubular cells expressed GM-CSF, a known STAT5 activator, and this pathway was required for in vitro alternative activation of macrophages by tubular cells. Furthermore, administration of a neutralizing antibody against GM-CSF after renal I/R attenuated kidney macrophage alternative activation and suppressed tubular proliferation. Taken together, these data show that tubular cells can instruct macrophage activation by secreting GM-CSF, leading to a unique macrophage reparative phenotype that supports tubular proliferation after sterile ischemic injury.

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Section: Discussionmentioning

confidence: 99%

GM-CSF Promotes Macrophage Alternative Activation after Renal Ischemia/Reperfusion Injury

Huen¹,

Huynh

Marlier³

et al. 2015

Journal of the American Society of Nephrology

101

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“…The study conducted by Malgorzata Sielska et al [20] revealed that autocrine GM-CSF had little or no effect on cell viability or the proliferation of glioma cells. There were also conflicting data implicating GM-CSF in the progression of a number of malignancies.…”

Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Intranasal GM-CSF enhances efficacy of local ACNU delivery rendezvousing with TMZ plus irradiation in glioblastoma

Yang¹,

Bu²,

Xue³

et al. 2018

Oncotarget

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This study aims to investigate the efficacy and safety of intranasal granulocytemacrophage colony stimulating factor (GM-CSF) treatment rendezvousing with chemoradiotherapy for post-operative glioblastoma patients. A total of ninety-two patients were randomized into two groups: control group (n = 46), patients who received radiotherapy with concomitant and adjuvant local delivery of nimustine hydrochloride (ACNU) rendezvousing with systemic administration of temozolomide (TMZ); observation group (n = 46), patients who received intranasal GM-CSF prior to each cycle of adjuvant chemotherapy based on the control group. Karnofsky performance status (KPS) scores, progression-free survival (PFS), overall survival (OS) and adverse effects were compared between these two groups. Two patients in the control group were excluded due to grade 3 hematologic toxicity. Furthermore, the observation group was superior to the control group with regard to PFS (7.8 months vs. 6.9 months, P = 0.016) and OS (19.2 months vs. 17.1 months, P = 0.045 without adjustment for interim analyses). KPS scores was higher in the observation group than in the control group after six months (84.35 ± 8.86, 80.65 ± 7.72; t = 4.552, P = 0.036). Neutropenia and thrombocytopenia decreased in the observation group, with incidences of 8.7% and 8.7%, respectively, when compared with the control group (29.5% and 18.2%, respectively; P = 0.012); while other adverse events were similar in both groups. Most adverse events were grade I-II and resolved spontaneously. Intranasal GM-CSF enhances the efficacy of the local delivery of ACNU rendezvousing with oral TMZ chemotherapy associated with significantly improved survival and quality of life in glioblastoma patients after surgery. This therapy could relieve chemotherapy related neutropenia, and does not increase the adverse events of other aspects.www.impactjournals.com/oncotarget/

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“…Additionally, TAM prime endothelial cells to sproute as they synthesize and release TNF-α and also other angiogenic molecules which have direct angiogenic effects or promote the secretion of vascular endothelial growth factor from glioma cells [140,101] ( Fig. 3).…”

Section: The Pro-angiogenic Role Of Myeloid Cells In Gliomasmentioning

confidence: 99%

CNS macrophages and peripheral myeloid cells in brain tumours

2014

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However, it is also becoming evident that some myeloid-directed glioma therapies may only be beneficial for distinct subclasses of gliomas and that a more cell-type specific manipulation of either microglia or macrophages may improve therapeutic outcome. 2 Neuropathological features of gliomasGlial tumours constitute approximately 50% of all newly diagnosed primary brain tumours, with low-grade gliomas accounting for roughly 15% of all brain tumours in adults [106]. The morphology and the cellular markers for gliomas share some similarities with the main macroglial cell-types (i.e. astrocytes, oligodendrocytes) [75].Histopathologically, gliomas are divided into four different grades (according to the classification scheme by the world health organization, WHO), in which low-grade tumours are defined as grade-I/-II and high-grade gliomas as grade-III and-IV [87]. The presence of mitotic activity is a key feature for distinguishing low-grade from high-grade gliomas [75]. Statistically, low-grade astrocytomas arise roughly in proportion to the relative mass of the different lobes with most common location within the frontal lobes, followed by temporal and parietal lobe lesions [107]. Overall, 5-and 10-year survival rates of ~70% and 50% for grade-I and grade-II gliomas, respectively, have been reported in the literature [25]. The tumour tissue has no obvious signs of neoangiogenesis, infiltrative invasion or inflammation [75]. On the contrary, the outlook for patients with high-grade gliomas is grim. The majority of individuals diagnosed with a grade-IV glioma, which are very heterogeneous tumours and therefore also named glioblastoma multiforme (GBM), have a median progression-free survival of just over half a year and median overall survival of 15-18 months [17], only some subpopulations of patients show median survivals of almost 2 years [54]. GBM is a fast growing, highly angiogenic and invasive tumour and the diffuse growth is a major obstacle for GBM therapy. Other hallmarks of malignant gliomas are break-down of the blood-brain barrier (BBB), many hypoxic areas and necrotic centres [75]. Gliomas are usually diagnosed by neurorimaging (i.e. magnetic resonance imaging) and visualisation of the uptake of a contrast-enhancing agent within the tissue indicates BBB-leakage/breakdown [159]. GBM typically presents as a ragged contrast-enhanced and complex multi-cystic structure. GBM may be diagnosed de novo, i.e. in patients without a clinical history for brain tumours (then named primary GBM) or may evolve from lower grade gliomas (secondary GBM) [103].3 Multi-modal glioma therapyGlioma therapy comprises very different strategies. For patients with deep-seated lesions or lesions located in eloquent regions which are clinically and radiographically indicated as low-grade glioma a conservative management including regular neuroimaging (after obtaining a histological diagnosis) [165], see also [130,150]. Individuals with high-grade gliomas undergo multi-modal treatment combining cytoreductive surgery, radiation-and ch...

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Distinct roles of CSF family cytokines in macrophage infiltration and activation in glioma progression and injury response

Cited by 132 publications

References 56 publications

GM-CSF Promotes Macrophage Alternative Activation after Renal Ischemia/Reperfusion Injury

GM-CSF Promotes Macrophage Alternative Activation after Renal Ischemia/Reperfusion Injury

WITHDRAWN: Intranasal GM-CSF enhances efficacy of local ACNU delivery rendezvousing with TMZ plus irradiation in glioblastoma

CNS macrophages and peripheral myeloid cells in brain tumours

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