Neutrophils in Gliomas

Massara, Matteo; Persico, Paola; Bonavita, Ornella; Poeta, Valeria Mollica; Locati, Massimo; Simonelli, Matteo; Bonecchi, Raffaella

doi:10.3389/fimmu.2017.01349

Cited by 108 publications

(117 citation statements)

References 67 publications

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“…The lymphocyte is the surrogate of an impaired cell‐mediated immunity, while neutrophil is acknowledged as a response to systematic inflammation . The recruitment of neutrophil and lymphocyte play a critical component in the pathogenesis of gliomas . Our study demonstrated that the counts of lymphocytes were significantly higher at early stage of glioma and then decreased with tumor progression.…”

Section: Discussionmentioning

confidence: 59%

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Peripheral blood test provides a practical method for glioma evaluation and prognosis prediction

et al. 2019

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Summary Objective To investigate the relationship between tumor characteristics and the preoperative counts of immune cells in peripheral blood test in glioma patients. Methods We included 260 WHO grades II‐IV patients who had preoperative peripheral blood test result from Sanbo hospital as training set. The 66 patients from Tiantan hospital was obtained for validation. RNA sequencing data from CGGA and TCGA datasets were used to evaluate the features of neutrophil subtype and lymphocyte subtype in glioma. Results We revealed that the count of preoperative lymphocytes, eosinophils and neutrophils were associated with glioma grades. Neutrophil‐to‐lymphocyte ratio (NLR) <3.2 was associated with better prognosis, whereas increased NLR was strongly corresponding with a poor prognosis. Lymphocyte type glioma patients demonstrated a positive correlation with isocitrate dehydrogenase (IDH) mutation and lower grade. IDH mutant glioma contained a higher proportion of tumor‐infiltrating lymphocytes than IDH wild‐type glioma. The immune subtype (neutrophil subtype and lymphocyte subtype) was an independent prognostic factor in glioma. Conclusion Our data demonstrated that NLR was an important prognostic factor in glioma. We classified that the immune subtype of glioma may contribute to a better understanding of disease pathogenesis and lead to the identification of new therapeutic targets for glioma patients.

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Section: Discussionmentioning

confidence: 59%

“…Nowadays, inflammation has been identified to be a hallmark of cancer and the critical role of inflammation components in glioma was a well‐established concept . Macrophages, T lymphocytes, and neutrophils were the important infiltrative inflammation cells in glioma microenvironment which could suppress or promote tumor progression …”

Section: Introductionmentioning

confidence: 99%

Peripheral blood test provides a practical method for glioma evaluation and prognosis prediction

et al. 2019

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“…Several possibilities emerge from our data to explain the reduction in PMN‐MDSCs. First, CXCL1 and CXCL2, which are major cancer‐related chemoattractants for these cells, were significantly attenuated in HuR KO TAMs in vivo and HuR KO PMG in vitro (Acharyya et al, ; Massara et al, ). In our prior work, we saw a marked decline in chemotaxis of neutrophils in vitro using conditioned media from HuR‐silenced PMG stimulated with LPS (Matsye et al, ).…”

Section: Discussionmentioning

confidence: 99%

Deletion of the RNA regulator HuR in tumor‐associated microglia and macrophages stimulates anti‐tumor immunity and attenuates glioma growth

Wang

Leavenworth

Hjelmeland

et al. 2019

Glia

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Glioblastoma is a malignant brain tumor that portends a poor prognosis. Its resilience, in part, is related to a remarkable capacity for manipulating the microenvironment to promote its growth and survival. Microglia/macrophages are prime targets, being drawn into the tumor and stimulated to produce factors that support tumor growth and evasion from the immune system. Here we show that the RNA regulator, HuR, plays a key role in the tumor‐promoting response of microglia/macrophages. Knockout (KO) of HuR led to reduced tumor growth and proliferation associated with prolonged survival in a murine model of glioblastoma. Analysis of tumor composition by flow cytometry showed that tumor‐associated macrophages (TAMs) were decreased, more polarized toward an M1‐like phenotype, and had reduced PD‐L1 expression. There was an overall increase in infiltrating CD4+ cells, including Th1 and cytotoxic effector cells, and a concomitant reduction in tumor‐associated polymorphonuclear myeloid‐derived suppressor cells. Molecular and cellular analyses of HuR KO TAMs and cultured microglia showed changes in migration, chemoattraction, and chemokine/cytokine profiles that provide potential mechanisms for the altered tumor microenvironment and reduced tumor growth in HuR KO mice. In summary, HuR is a key modulator of pro‐glioma responses by microglia/macrophages through the molecular regulation of chemokines, cytokines, and other factors. Our findings underscore the relevance of HuR as a therapeutic target in glioblastoma.

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“…Gliomas are the most common type of primary brain tumours in adults and differ in the malignancy grade. 33 The number of neutrophils infiltrating the tumour correlates with the severity of the disease. [30][31][32] The ways to decrease the tumour progression are intensively studied nowadays, since this is associated with an increase in the lifespan of patients.…”

Section: Discussionmentioning

confidence: 99%

“…30 A poor prognosis with a short survival time is observed for patients with glioma developing to the highest degree of malignancy and passes into glioblastoma. 33,34 It has been shown that these cells can play a dual role in tumour development: both protumour and antitumour. An important role in the regulation of gliomas' malignancy is attributed to neutrophils.…”

Section: Discussionmentioning

confidence: 99%

2‐Hexadecenal inhibits growth of C6 glioma cells

Семенкова

Kvacheva

Lisovskaya

et al. 2019

Cell Biochemistry & Function

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2-Hexadecenal (2HD) formation in the organism occurs via irreversible enzymatic degradation of sphingosine-1-phosphate or nonenzymatic γ-, UV-, or HOCl-induced destruction of a number of sphingolipids including S1P. The current research focuses on the study of 2HD effects on C6 glioma cells growth. The results obtained show that 2HD causes a dose-dependent decrease in proliferative and mitotic indices.The change in the mitotic index is due to the redistribution of cells in the different phases of mitosis. These processes are accompanied by cytoskeleton rearrangement and changes in cell morphology, which are expressed in F-actin redistribution, change in the number and type of filopodia and fibrils, leading to cell shape changes, decrease in intercellular contacts and monolayer rarefaction. Cells treatment with 2HD leads to apoptosis induction and signalling pathways modification, including activation of JNK, p38, and ERK1/2 MAPK but not PI3K. The effects observed are not related to the cytotoxicity of 2HD. Significance of the study: 2HD-an unsaturated aldehyde, which level can rise under conditions of oxidative stress as a result of nonenzymatic sphingolipids' destruction. The mechanisms of 2HD action on various cell types have not been sufficiently studied. Therefore, the study on functional role of this aldehyde in different cell types that may be its target is relevant. This study demonstrated that 2HD inhibits growth of C6 glioma cells due to modification of intracellular processes of signal transduction, cytoskeleton rearrangement, change in the mitotic regimen and apoptosis induction.

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Neutrophils in Gliomas

Cited by 108 publications

References 67 publications

Peripheral blood test provides a practical method for glioma evaluation and prognosis prediction

Peripheral blood test provides a practical method for glioma evaluation and prognosis prediction

Deletion of the RNA regulator HuR in tumor‐associated microglia and macrophages stimulates anti‐tumor immunity and attenuates glioma growth

2‐Hexadecenal inhibits growth of C6 glioma cells

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