AUTHOR=Ji Hang , Liu Zhihui , Wang Fang , Sun Haogeng , Wang Nan , Liu Yi , Hu Shaoshan , You Chao 

TITLE=Novel macrophage-related gene prognostic index for glioblastoma associated with M2 macrophages and T cell dysfunction

JOURNAL=Frontiers in Immunology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.941556

DOI=10.3389/fimmu.2022.941556

ISSN=1664-3224

ABSTRACT=This study aims to construct a macrophage-related prognostic index (MRGPI) for glioblastoma (GBM) and explore the underlying molecular, metabolic, and immunological features. Based on the GBM dataset from The Cancer Genome Atlas (n = 156), 13 macrophage-related hub genes were identified by weighted gene co-expression network (WGCNA) analysis. Five prognostic genes identified by multivariate cox regression model were used to construct a prognostic MRGPI, which was further validated by another two cohorts. Thereafter, the molecular, metabolic, and immune features and the benefit of ICI in MRGPI-based groups were comprehensively characterized. The MRGPI was constructed using GPR84, NCF2, HK3, LILRB2, and CCL18. The MRGPI-high group had an unfavorable overall survival (OS) and progression-free interval (PFI). Besides, immune-related pathways and activated eicosanoid metabolic pathways were enriched in the MRGPI-high group.  An increased proportion of alternatively activated tumor-associated macrophages was found in the MRGPI-high group, which was associated with T cell dysfunction and patient inclination to benefit from immune check point inhibitors (ICI) like anti-PD1 therapy. In contrast, the IRGPI-low group was less immune active but had a favorable outcome. Together, we have developed a promising biomarker to classify the prognosis, metabolic and immune features for GBM, and provide references for facilitating the personalized application of ICI in GBM.