Immune Heterogeneity of Glioblastoma Subtypes: Extrapolation from the Cancer Genome Atlas

  title={Immune Heterogeneity of Glioblastoma Subtypes: Extrapolation from the Cancer Genome Atlas},
  author={Tiffany A Doucette and Ganesh Rao and Arvind U. K. Rao and Li Shen and Kenneth D. Aldape and Jun Wei and Kristine Dziurzynski and Mark R. Gilbert and Amy B. Heimberger},
  journal={Cancer Immunology Research},
  pages={112 - 122}
Doucette and colleagues analyzed The Cancer Genome Atlas glioblastoma database and found differential expression of distinct glioma antigens and immunosuppressive and effector genes among the glioblastoma subtypes, which may influence responses to immune therapeutic strategies in patients. Purpose: The molecular heterogeneity of glioblastoma has been well recognized and has resulted in the generation of molecularly defined subtypes. These subtypes (classical, neural, mesenchymal, and proneural… 

Figures and Tables from this paper

Immune Microenvironment in Glioblastoma Subtypes

The origin, features, and functions of TAMs in distinct GBM subtypes are reviewed and prospects of therapeutically targeting TAMs to increase the efficacy of T-cell functions are discussed.

Tumor evolution of glioma intrinsic gene expression subtype associates with immunological changes in the microenvironment

This study provides a comprehensive transcriptional and cellular landscape of IDH wild type GBM during treatment modulated tumor evolution, including a definition of tumor-intrinsic gene expression subtypes and how they relate to the different cellular components of the tumor immune environment.

Improved prognostication of glioblastoma beyond molecular subtyping by transcriptional profiling of the tumor microenvironment

By combining molecular subtyping with gene expression measures of tumor infiltration, the present work contributes with improving prognostic models in GBM and identifies a subset of GBM samples with significantly higher abundances of most immune and stromal cells.

Molecular Heterogeneity of Glioblastoma and its Clinical Relevance

Intra-tumor heterogeneity of molecular genetic profiles in glioblastoma may explain the difficulties encountered in the validation of oncologic biomarkers, and contribute to a biased selection of patients for single target therapies, treatment failure or drug resistance.

Human Mesenchymal glioblastomas are characterized by an increased immune cell presence compared to Proneural and Classical tumors

Investigating differences in immune cell subpopulations among distinct transcriptional subtypes of GBM demonstrated that molecularly distinct GBM subtypes are characterized by profound differences in the composition of their immune microenvironment, which could potentially help to identify tumors amenable to immunotherapy.

Glioblastoma cancer stem cells: Biomarker and therapeutic advances

Global immune fingerprinting in glioblastoma reveals immune-suppression signatures associated with prognosis

This work integrated multi-parameter flow cytometry and mass cytometry time of flight analysis of patient blood to determine changes in the immune system among tumor types and over disease progression and found that increased numbers of MDSCs in recurrent GBM portended poor prognosis.

Immune landscapes associated with different glioblastoma molecular subtypes

The results of this study offer a comprehensive analysis of the distribution and the infiltration of the immune components across the four commonly described GBM subgroups, setting the basis for a more detailed patient classification and new insights that may be used to better apply or design immunotherapies for GBM.

PD-L1 tumor expression is associated with poor prognosis and systemic immunosuppression in glioblastoma

The data points to a putative role for PD-L1 expression in glioblastoma biology, which correlates to poor patient overall survival, as well as with a general systemic inflammatory status and immunosuppression.

Transcriptional signatures in histologic structures within glioblastoma tumors may predict personalized drug sensitivity and survival

The cellular tumor is identified as a glioblastoma structure that can be targeted for transcriptional analysis to more accurately stratify patients by subtype and prognosis, and an improved risk stratification gene signature is created.



Immune genes are associated with human glioblastoma pathology and patient survival

The co-expression network analysis of the immune genes disclosed 6 powerful modules identifying innate immune system and natural killer cells, myeloid cells and cytokine signatures that demonstrates the immune signatures found in previous GBM genomic analyses and suggests the involvement of immune cells in GBM biology.

Gene Expression Profile Correlates with T-Cell Infiltration and Relative Survival in Glioblastoma Patients Vaccinated with Dendritic Cell Immunotherapy

The results suggest that the mesenchymal gene expression profile may identify an immunogenic subgroup of glioblastoma that may be more responsive to immune-based therapies.

Antigenic Profiling of Glioma Cells to Generate Allogeneic Vaccines or Dendritic Cell–Based Therapeutics

Purpose: Allogeneic glioma cell lines that are partially matched to the patient at class I human leukocyte antigen (HLA) loci and that display tumor-associated antigens (TAA) or antigenic precursors

Challenges in Immunotherapy Presented by the Glioblastoma Multiforme Microenvironment

Many of the current approaches to immunotherapy for GBM are discussed and the challenges presented by the tumor microenvironment are focused on.

Glioblastoma Cancer-Initiating Cells Inhibit T-Cell Proliferation and Effector Responses by the Signal Transducers and Activators of Transcription 3 Pathway

Findings indicate that cancer-initiating cells contribute to the immune evasion of GBM and that blockade of the STAT3 pathway has therapeutic potential.

Molecular subclassification of diffuse gliomas: Seeing order in the chaos

While the unprecedented level of newly available molecular profiling data may seem at first to needlessly balkanize and complicate glioma subclassification, these analyses are in fact providing a more unified picture of key pathogenetic routes and potential avenues for therapeutic intervention.

Greater chemotherapy-induced lymphopenia enhances tumor-specific immune responses that eliminate EGFRvIII-expressing tumor cells in patients with glioblastoma.

A phase II, multicenter trial was undertaken to assess the immunogenicity of an experimental EGFRvIII-targeted peptide vaccine in patients with GBM undergoing treatment with serial cycles of standard-dose (STD) or dose-intensified (DI) TMZ, which induces patient immune responses despite therapeutic TMZ-induced lymphopenia and eliminates EGFR vIII-expressing tumor cells without autoimmunity.

Intratumoral Mediated Immunosuppression is Prognostic in Genetically Engineered Murine Models of Glioma and Correlates to Immunotherapeutic Responses

These murine model systems are more suitable for testing therapeutics, especially immunotherapeutics, in the context of translational studies, because their clonotypic nature does not recapitulate the heterogeneous biology and immunosuppressive mechanisms of humans.

The Incidence, Correlation with Tumor-Infiltrating Inflammation, and Prognosis of Phosphorylated STAT3 Expression in Human Gliomas

Purpose: The signal transducer and activator of transcription 3 (STAT3) is frequently overexpressed in most cancers, propagates tumorigenesis, and is a key regulator of immune suppression in cancer