Improving Responses to Immunotherapy in Glioblastoma Multiforme

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About this Research Topic

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Background

Glioblastoma multiforme (GBM) is a uniformly fatal primary brain tumour. Whilst many therapeutic interventions have been studied pre-clinically very few new therapies have been approved for the use of GBM therapy.

These tumours present a unique challenge due to their location within the brain, making delivery of therapeutic interventions challenging. Active immunotherapy represents an attractive avenue for therapy, with activated immune cells being shown to cross the blood brain barrier and penetrate brain tumours. Despite several advances being made in numerous other cancer types, many immunotherapeutic interventions in GBM have failed to make it past phase 3 clinical trials and as of now (2022) no immunotherapeutic interventions have been approved for the therapy of GBM.

Whilst the location of these tumours makes them incredibly hard to treat, they are also known to be highly immunosuppressive making them difficult to target with immunotherapy, potentially explaining the failures seen in these clinical trials. GBM tumours are known to have a low mutational burden relative to other cancers and they create a hostile environment for infiltrating immune cells via the expression of immunosuppressive checkpoint molecules and cytokines within the tumour microenvironment. GBM tumours also contain many immunosuppressive cells such as regulatory T-cells, myeloid derived suppressor cells and M2 macrophages which further act to reduce the anti-tumour immune response. When targeting these tumours with immunotherapy it is important to factor in the tumour microenvironment and its immunosuppressive effects for immunotherapy to have the highest efficacy.

In this research topic we welcome contributions from authors who are looking at improving immunotherapies in the GBM setting, whether this be novel immunotherapies, neoadjuvant therapy, selecting patients based on gene expression profile, examining microbiota when measuring immunotherapy response, combinatorial therapy, or combining standard therapies with immunotherapy with the aim of boosting the anti-tumour immune response. Contributions considered for this research topic include original articles, clinical trials and review articles focusing on:

1. Novel immunotherapeutic approaches
1.1. Neoadjuvant therapy
1.2. Novel delivery systems
1.3. Targeting the tumour microenvironment
1.4. Oncolytic virotherapy
1.5. CAR cells
1.6. Reprogramming immunosuppressive cells

2. Combination therapies
2.1. Standard therapy
2.2. Checkpoint inhibitors
2.3. Small molecule inhibitors
2.4. Metabolic alteration

3. The impact of gene expression profile
3.1. Predictors of immunotherapy response
3.2. Targetable genes

4. The impact of microbiota on immunotherapy
4.1. Predictors of immunotherapy response
4.2. Microbiome alteration in combination with immunotherapy

Manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this topic.

Topic Editor Michael Barish received financial support from Chimeric Therapeutics (Australia). The other Topic Editors declare no competing interests with regard to the Research Topic subject.

Keywords: GBM, novel immunotherapeutic interventions, Micro-environment, immune-suppressive cells, microbiota, novel combinatorial approaches, novel vaccines, immunotherapy, metabolic alteration, predictor of immune response.

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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