Background: Gliomas are the most common solid malignant tumors of the brain; diffuse gliomas pose a remarkable conundrum on treatment strategy. WHO Grade IV (Glioblastomas) delineate a refractory resistance to treatment even with standard combination regimen therapy of surgery, chemotherapy and radiation therapy causing increased recurrence rate with a median survival of less than one year. Management of gliomas is precluded by several factors including intra and inter tumoral heterogeneity, genomic landscape and microenvironment immunosuppression ability, which spell the inflicted pathways that counteract the therapeutic interventions. This is systematic review aiming to evaluate the effect of Tumor Mutation Burden (TMB) and Tumor Microenvironment (TME) as biomarkers of treatment outcome and prognosis of gliomas. Methods and Analysis: This systematic Review and Meta-analysis will consider the PRISMA 2020 guideline correspondence. For source of literature evidence several electronic databases including EMBASE, PubMed, Cochrane Library, SCOPUS, Web of Science, Semantic Scholar and Google scholar will be searched. All non-RCTs peer reviewed original research articles addressing the prognostic role of tumor mutation burden, tumor mutation pathways, microenvironment will be included, and data will be extracted using the Ms Excel Sheets. Studies with homogeneity and low risk of bias according to NOS 4-9 will constitute a Meta-analysis for evaluating the effect of TMB, Mutation pathways and Microenvironment for treatment outcome and prognosis of glioma. Ethical Consideration and Dissemination: Ethical approval does not apply for there is no human participant involvement in this review study .The findings of this study will be disseminated at scientific conferences and the manuscript for publication will be submitted for publication to a reputable peer reviewed journal of Neurosurgery. This review was registered at PROSPERO CRD42022377829.

Background Gliomas are the most common solid malignant tumors of the brain; diffuse gliomas pose a remarkable conundrum on treatment strategy. WHO Grade IV (Glioblastomas) delineate a refractory resistance to treatment even with standard combination regimen therapy of surgery, chemotherapy and radiation therapy causing increased recurrence rate with a median survival of less than one year(1). Management of gliomas is precluded by several factors including intra and inter tumoral heterogeneity, genomic landscape and microenvironment immunosuppression ability, which spell the inflicted pathways that counteract the therapeutic interventions. This is systematic review aiming to evaluate the effect of tumor mutation burden (TMB) and Tumor microenvironment (TME) as biomarkers of treatment outcome and prognosis of gliomas. Methods and Analysis This systematic Review and Meta –analysis will consider the PRISMA 2020 guideline correspondence. For source of literature evidence several electronic databases including EMBASE, PubMed, Cochrane Library, SCOPUS, Web of Science, Semantic Scholar and Google scholar will be searched. All non-RCTs peer reviewed original research articles addressing the prognostic role of tumor mutation burden, tumor mutation pathways, microenvironment will be included, and data will be extracted using the Ms Excel Sheets. Studies with homogeneity and low risk of bias according to NOS 4–9 will constitute a Meta-analysis for evaluating the effect of TMB, Mutation pathways and Microenvironment for treatment outcome and prognosis of glioma. Ethical Consideration and Dissemination Ethical approval does not apply for there is no human participant involvement in this review study .The findings of this study will be disseminated at scientific conferences and the manuscript for publication will be submitted for publication to a reputable peer reviewed journal of Neurosurgery. This review was registered at PROSPERO CRD42022377829