Transcriptional characterization of immunological infiltrates and their relation with glioblastoma patients overall survival

Abstract

: Several cell populations from the peripheral immune system interact to create a complex immunologic status during glioblastoma growth and response to therapy. The aim of this study was to integrate the impact of different immune cell populations present in glioblastoma tumor microenvironment on overall survival. : Gene expression and clinical data were generated by The Cancer Genome Atlas and previously reported meta-signatures representing cells of the immune system were used. The relationship between meta-signatures was evaluated through Pearson's correlation analyses. Survival analyses were performed through Kaplan-Meier plots and Cox regression model.: Meta-signatures corresponding to infiltrating immune cells with immunosuppressive roles, such as macrophages, NK and NK T cells, MDSCs and Tregs, correlated with poorer patient prognosis. Meta-signatures related to CD8+ T cells predicted improved survival only in patients with low immunosuppressive meta-signatures. By clustering the meta-signatures we found that the cluster containing high meta-signatures of macrophages, MDSCs and Tregs demonstrated the worst prognosis. : Integrating the information provided by transcriptional signatures of immunological aspects is fundamental in understanding the impact of the immune system on patient survival. We found a predictive impact on survival with positive role for CD8 and negative roles for macrophages, MDSC, Tregs, NK and NK-T in glioblastoma patients. Understanding these regulatory and stimulatory factors of patients' immune system is essential to delineate an effective strategy to increase the anti-tumor immune response and to generate potential clinical benefits.

Development of an Immune Infiltration-Related Prognostic Scoring System Based on the Genomic Landscape Analysis of Glioblastoma Multiforme

“…Therefore, reversing the immunosuppressive microenvironment caused by macrophages may be promising therapies in GBM. Previous bioinformatics analysis showed that macrophages play a negative role, while CD8+ T cells play a positive role in survival prediction of GBM patients (27). Pan-cancer analysis also revealed that several T cells, including gamma delta and CD8+ T cells, are broadly favorable prognostic signatures (28).…”

Immune cell infiltration as a biomarker for the diagnosis and prognosis of digestive system cancer

“…Macrophages, as important cells of the immune system, show different genotypes and functions in different microenvironments . Pereira et al revealed the landscape of glioblastoma, showing that patients can be clustered in different subtypes with M0 and M2 macrophages representing major contributors to the tumor microenvironment. Xiong et al found that M2 macrophages were the independent prognostic factors in colorectal cancer by univariate and multivariable Cox regression analysis.…”

“…CIBERSORT contains 547 genes and is highly sensitive and specific to 22 phenotypes of human immune cells, which can properly determine the diversity and landscape of tumor‐infiltrating immune cells. Because of the superior performance of CIBERSORT, increasing attention has been aroused in many studies on the tumor microenvironment …”

Comprehensive genomic profiling of glioblastoma tumors, BTICs, and xenografts reveals stability and adaptation to growth environments

“…Th1 cells are thought to be tumor-suppressing by playing a role in activating cytotoxic cells (25). The effect of the immune microenvironment on glioma progression has been known for some time and has implications for treatment improvement and survival (26)(27)(28)(29)(30)(31), and therefore the use of expression-based cell deconvolution and enrichment analyses of the tumor microenvironment may help to reveal novel pathways for targeted treatment via immune modulation.…”