Microglial action in glioma: A boon turns bane

Ghosh, Anirban; Chaudhuri, Swapna

doi:10.1016/j.imlet.2010.03.003

Cited by 44 publications

(32 citation statements)

References 78 publications

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“…These results suggest that microglial cells contribute to the chemo-and radio-resistant phenotype of gliomas. Previous studies reported correlation of microglial invasion with aggressiveness and poor prognosis in gliomas by releasing growth promoting, angiogenic, and immunosuppressive factors (37)(38)(39)(40). Our results suggest that infiltrating microglial cells may shape the tumor microenvironment to not only negatively influence the natural course of disease but also the response to therapy.…”

Section: Discussionsupporting

confidence: 55%

The Endogenous Tryptophan Metabolite and NAD+ Precursor Quinolinic Acid Confers Resistance of Gliomas to Oxidative Stress

et al. 2013

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Quinolinic acid is a product of tryptophan degradation and may serve as a precursor for NAD þ , an important enzymatic cofactor for enzymes such as the DNA repair protein PARP. Pathologic accumulation of quinolinic acid has been found in neurodegenerative disorders including Alzheimer and Huntington disease, where it is thought to be toxic for neurons by activating the N-methyl-D-aspartate (NMDA) receptor and inducing excitotoxicity. Although many tumors including gliomas constitutively catabolize tryptophan, it is unclear whether quinolinic acid is produced in gliomas and whether it is involved in tumor progression. Here, we show that quinolinic acid accumulated in human gliomas and was associated with a malignant phenotype. Quinolinic acid was produced by microglial cells, as expression of the quinolinic acid-producing enzyme 3-hydroxyanthranilate oxygenase (3-HAO) was confined to microglia in glioma tissue. Human malignant glioma cells, but not nonneoplastic astrocytes, expressed quinolinic acid phosphoribosyltransferase (QPRT) to use quinolinic acid for NAD þ synthesis and prevent apoptosis when de novo NAD þ synthesis was blocked.Oxidative stress, temozolomide, and irradiation induced QPRT in glioma cells. QPRT expression increased with malignancy. In recurrent glioblastomas after radiochemotherapy, QPRT expression was associated with a poor prognosis in two independent datasets. Our data indicate that neoplastic transformation in astrocytes is associated with a QPRT-mediated switch in NAD þ metabolism by exploiting microglia-derived quinolinic acid as an alternative source of replenishing intracellular NAD þ pools. The elevated levels of QPRT expression increase resistance to oxidative stress induced by radiochemotherapy, conferring a poorer prognosis. These findings have implications for therapeutic approaches inducing intracellular NAD þ depletion, such as alkylating agents or direct NAD þ synthesis inhibitors, and identify QPRT as a potential therapeutic target in malignant gliomas. Cancer Res; 73(11); 3225-34. Ó2013 AACR.

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Section: Discussionsupporting

confidence: 55%

The Endogenous Tryptophan Metabolite and NAD+ Precursor Quinolinic Acid Confers Resistance of Gliomas to Oxidative Stress

et al. 2013

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“…One among many astonishing facts of glioma is that, unlike other organ-specific neoplasms, glioma not only escapes the immune system of the CNS but it also often manipulates the immunological cells in the course of its progression. Microglia or the brain macrophage might get influenced to secrete effective substances to reach to the glioma cell patch dissolving the eCM of the brain tissue through, but unwillingly they indirectly help glioma cells in their metastatic invasion through the damaged eCM done by themselves [98] . Indeed the presence and commemoration of brain macrophage or microglia ( Figure 5) might lead to the better efficacy of glioma lethality [99] .…”

Section: Glioma Progression: Cellular Niche Redefinedmentioning

confidence: 99%

Glia to glioma: A wrathful journey

Ghosh¹,

Bhattacharjee

Ghosh

et al. 2017

Adv Mod Oncol Res

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Glial cells, unlike neurons in the brain, can undergo cellular division to maintain their functional continuity. However, sometimes this divisional attribute gets uncontrolled, which breaches tissue organization and transforms tissues into neoplasm. The proliferative abnormality of neuroglia results in one of the most dreaded neoplasm accounting for about 30% of all brain tumors-the glioma. The abnormal proliferation, high level of progression and invasive potential makes glioma one of the most lethal killers in its class. The pathological scenario becomes more moribund owing to poor prognosis and high mortality rate of the menace. Conventional onco-therapies yield dismal results compared to other soft tissue tumors. In time, with the advent of newer trends of prognosis and treatment modalities in the field of oncology, a hope for betterment is expected, but not yet achieved. These advancements would fetch some better results with proper and minute understanding of the biology of glioma, both at physiological as well as molecular level. In the present context, we have tried to document an insight to glioma biology that can serve as a primer to understand this lethal killer and its killing spree, with some approaches to combat its carnage.

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“…Particularly, proinflammatory cytokines including IL-1 , IL-6, TNF could not be sufficiently released to launch substantial innate immune function against glioma, however their phagocytic function was not impaired and also exhibited low level of non-specific cytotoxicity (Hussain et al, 2006b). In rodent glioma model lack of proinflammatory cytokines IFN , IL-12 and IL-6, and conversely cumulative dominance of IL-4 and IL-10 favoring the suppression of immune response was recently observed (Ghosh et al, 2010). Microglial activity stature was also reflected in their morphometry in scanning electron microscopy (SEM), where their filapodial extensions, sizes and shapes had shown noticeable alterations (Begum et al, 2003).…”

Section: Glioma Antigen Presentation By Microgliamentioning

confidence: 99%

“…Then the infiltrated lymphocytes may come across the APC present in the brain parenchyma or at the site of pathogenesis. The T cell-microglia interactions in CNS autoimmune encephalomyelitis (EAE) or brain tumor; T cell secretion of Th1 cytokines to mature microglia as functional APC and resulting restimulation of leukocytes by them; counter regulation of this inflammation by Th2 induction by microglia etc had been detailed mostly on the functional studies committed so far (Aloisi et al, 2000;Ghosh & Chaudhuri, 2010).…”

Section: Lymphocytes Assess Cns Antigen and Enter Into Neuropil 231mentioning

confidence: 99%

“…In this process peripheral APC in brain and 'so called' resident microglia as well as DCs also play very important role. The role of local APC in glioma immunity has been detailed by Ghosh and Chaudhuri with a new outlook to explain the contradiction of glioma promoting role of microglia (Ghosh and Chaudhuri, 2010).These myeloid cell populations have the potential to act as chief immunomodulator in brain by surveillance in the tissue environment, guiding the leukocytes in CNS and simultaneously exerting effector function to neoplastic cells. The damaging activities of the cell are probably their own misfired 'goodness' or their potential that is misled by glioma cells.…”

Section: Conclusion: Future Immuno-therapeutics Must Capitalize This mentioning

confidence: 99%

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