The Process and Regulatory Components of Inflammation in Brain Oncogenesis

Abstract

Central nervous system tumors comprising the primary cancers and brain metastases remain the most lethal neoplasms and challenging to treat. Substantial evidence points to a paramount role for inflammation in the pathology leading to gliomagenesis, malignant progression and tumor aggressiveness in the central nervous system (CNS) microenvironment. This review summarizes the salient contributions of oxidative stress, interleukins, tumor necrosis factor-α(TNF-α), cyclooxygenases, and transcription factors such as signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB) and the associated cross-talks to the inflammatory signaling in CNS cancers. The roles of reactive astrocytes, tumor associated microglia and macrophages, metabolic alterations, microsatellite instability, O6-methylguanine DNA methyltransferase (MGMT) DNA repair and epigenetic alterations mediated by the isocitrate dehydrogenase 1 (IDH1) mutations have been discussed. The inflammatory pathways with relevance to the brain cancer treatments have been highlighted.

Astrocytes, the rising stars of the glioblastoma microenvironment

“…In the same way, an STAT‐3 expressing subpopulation of reactive astrocytes has been showed to modulate the immune process in the brain during metastasis, thus promoting tumor cells survival and consequently decreasing patients' survival (Priego et al, ). Altogether, those reports highlight the potential of TAAs to protect GBM cells against anti‐cancer immune reaction by secreting now well‐described anti‐inflammatory factors (Mostofa, Punganuru, Madala, Al‐Obaide, & Srivenugopal, ).…”

AVNP2 protects against cognitive impairments induced by C6 glioma by suppressing tumour associated inflammation in rats

“…Arrow (5) indicated that AVNP2 could suppress the level of pro-inflammation cytokines and protects against cognitive impairment. of related signalling pathways promote cognitive impairment in patients with brain tumours (Mostofa et al, 2017).…”

“…Modulating the local inflammatory response has become a new strategy for immunotherapy due to its vital role in the development of tumours (Graf et al, 2002;Mineharu et al, 2011). Proinflammatory cytokines, including interleukin-6 (IL)-6, IL-1β and tumour necrosis factor-α (TNF)-α that promote tumour proliferation and migration and NF-ĸB pathway play important roles in this process (Mostofa et al, 2017;McFarland et al, 2013;Myung et al, 2010). Therefore, drugs and related therapies devoted to modulating peri-tumour inflammation in the treatment of glioblastoma have massive potential both now and in the future.…”

The Impact of Everyday Stressors on the Immune System and Health

“…While much initial work focused on direct effects of catecholamines and other stress mediators on cancer progression, subsequent work identified that the tumor microenvironment is a critical regulator of cancer progression and metastasis (Landskron et al 2014;Wang et al 2017;Berghoff and Preusser 2015). The tumor microenvironment has a pivotal role in regulating tumor cell growth, invasion, and metastasis, specifically through reciprocal cross-talk with infiltrating immune cells (lymphocytes, neutrophils, and macrophages), endothelial cells, mesenchymal stromal cells (fibroblasts and myofibroblasts), and their secretory products, all of which can modulate gene expression and alter the behavior of tumor cells (Mostofa et al 2017).…”