en Clinical Neuroscience Clinical Neuroscience Review Article <h4 style="text-align: justify;"><span style="font-size:14px;"><span style="font-family:Tahoma;"><span style="line-height:2;"><span lang="EN">One of the most significant health issues facing the world today is glioma and glioblastoma multiforme (GBM), which is a primary brain tumor regardless of the progress made in treatment modalities. Gliomas develop depending on the glial cells and represent about 80 percent of malignant brain tumors and GBM consists of 50-60 percent of cases. Immune and inflammatory cells, especially microglia, are abundant in the TME in glioma that are major contributors to tumor development and resistance to therapy. This narrative review will look into the neuroimmune interactions that affect tumor growth, immune infiltration, and response to treatments and particularly the role of microglia and polarization. The microglia can have two distinct impacts on the tumor behavior, which are contingent on their pro-inflammatory (M1) or anti-inflammatory (M2) phenotype. Glioma cells produce mediators which selectively differentiate microglia into the M2 phenotype enhancing tumor growth, angiogenesis, and immunity. Despite molecular pathways that control microglial polarization, which have potential therapeutics, the complexity of the TME is an obstacle to successful clinical implementation. This is a synthesis review of existing evidence, and it is important to note that the current therapeutic approaches require more advanced methods, such as high-resolution spatial profiling, drugs that can penetrate the blood-brain barrier, and computational analysis of individual cells to find biomarkers that can be acted upon. Neuroimmune interaction through reformulation of treatment approaches can promote long term results in management of primary brain tumors.</span></span></span></span></h4> Primary brain tumors, Glioblastoma multiforme (GBM), Gliomas, Tumor-associated macrophages (TAMs), Neuroimmunology 26 40 http://neuroupdates.de/browse.php?a_code=A-10-1-64&slc_lang=en&sid=1 Parvin Mozafari Parvinmozaffari73@gmail.com 1003194753284600434 0009-0002-8107-2390 No Faculty of medicine, University of Georgia, Tbilisi, Georgia Ragd Khalid Hassan Babiker ragdkhalid6@gmail.com 1003194753284600435 0009-0007-7571-6563 No School of Medicine, Caucasus university, Tbilisi, Georgia Tinatin Jojua Tikajojua1@gmail.com 1003194753284600436 0009-0009-3006-9176 Yes Faculty of Medicine, Tbilisi State Medical University, Tbilisi, Georgia Daviti Jishkariani Jishkarianid9@gmail.com 1003194753284600437 0009-0004-7575-7515 No Faculty of Medicine, Tbilisi State Medical University, Tbilisi, Georgia Mohammad Hassan Bagheri hassanbagheri2002@gmail.com 1003194753284600438 0009-0000-5578-3215 No Tehran University of Medical Sciences, Tehran, Iran