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Immune microenvironments differ in immune characteristics and outcome of glioblastoma multiforme

ABSTRACT: Understanding the interactions between tumors and the host immune system holds great promise to uncover biomarkers for targeted therapies, predict the prognosis of patients and guide clinical treatment. However, the immune signatures of glioblastoma multiforme (GBM) remain largely unstudied in terms of systematic analyses. We aimed to classify GBM samples according to immune-related genes and complement the existing immunotherapy system knowledge. In this study, we designed a strategy to identify 3 immune subtypes representing 3 different immune microenvironments (M1-M3) and associated with prognosis. The three subtypes were significantly different in terms of specific immune characteristics (immune cell subpopulations, immune responses, immune cells and checkpoint gene interactions). In additional, somatic alterations and methylation changes were identified that correlated with genes related to a worse prognosis subtype in the microenvironment. More importantly, in M3 (worst prognosis subtype) and M2 (best prognosis subtype), the interaction between immune cells and checkpoint genes was different, and this had an important effect on the prognosis. Finally, we used risk scores of immune cells and checkpoint genes to evaluate the prognosis of GBM patients and validated the results with 3 independent datasets. Disordered interactions between immune cells and checkpoint genes result in a change in the immune microenvironment and affects the prognosis of patients. We propose that a better understanding of the immune microenvironment of advanced cancers may provide new insights into immunotherapy.

ORGANISM(S): Homo sapiens

PROVIDER: GSE122586 | GEO | 2019/06/20

REPOSITORIES: GEO

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Project description:Molecular subtyping is expected to enable bladder cancer (BC) precise treatment. However, reliable subtyping strategies for clinical application remains defective and controversial. Given the significance of tumor immune dysfunction and exclusion (TIDE) in tumor immune escape and immunotherapy, we aimed to develop a novel TIDE-based subtyping method to facilitate personalized management. Transcriptome data of BC was used to evaluate the heterogeneity and the status of TIDE patterns. We identified 69 TIDE biomarker genes and classified BC samples into three subtypes using consensus clustering. Subtype I showed the lowest TIDE status and malignancy with the best prognosis and highest sensitivity to immune checkpoint blockade (ICB) treatment, which was enriched of metabolic related signaling pathways. Subtype III represented the highest TIDE status and malignancy with the poorest prognosis and resistance to ICB treatment, resulting from its inhibitory immune microenvironment and T cell terminal exhaustion. Subtype II was in a transitional state with intermediate TIDE level, malignancy, and prognosis. We further confirmed the existence and characteristics of our novel TIDE subtypes using real-world BC samples. This subtyping method was proved to be more efficient than previous known methods in identifying non-responders to immunotherapy. We also propose that combining our TIDE subtypes with known biomarkers can potentially improve the sensitivity and specificity of these biomarkers. Moreover, besides guiding ICB treatment, this classification approach can assist in selecting the frontline or recommended drugs. Finally, we confirmed that the TIDE subtypes are conserved across the pan-tumors. In conclusion, our novel TIDE-based subtyping method can serve as a powerful clinical tool for BC and pan-cancer patients, and potentially guiding personalized therapy decisions for selecting potential beneficiaries and excluding resistant patients of ICB therapy.

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Immune microenvironments differ in immune characteristics and outcome of glioblastoma multiforme

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