Prospect of Immunotherapy for Glioblastoma: Tumor Vaccine, Immune Checkpoint Inhibitors and Combination Therapy

Ishikawa, Eiichi; Yamamoto, Tetsuya; Matsumura, Akira

doi:10.2176/nmc.nmc.ra.2016-0334

Cited by 17 publications

(16 citation statements)

References 73 publications

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“…Gliomas treated with DC vaccination ± murine anti–PD-1 monoclonal antibody blockade or a colony-stimulating factor 1 receptor inhibitor (PLX3397) had prolonged survival in vivo [ 74 ]. Previous studies indicate that combination therapy with immune checkpoint blockade is effective for the treatment of malignant tumors, including GBM [ 75 , 76 ].…”

Section: Discussionmentioning

confidence: 99%

YTHDF2 correlates with tumor immune infiltrates in lower-grade glioma

Lin

Wang²,

Yang³

et al. 2020

Aging

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Immunotherapy is an effective treatment for many cancer types. However, YTHDF2 effects on the prognosis of different tumors and correlation with tumor immune infiltration are unclear. Here, we analyzed The Cancer Genome Atlas and Gene Expression Omnibus data obtained through various web-based platforms. The analyses showed that YTHDF2 expression and associated prognoses may depend on cancer type. High YTHDF2 expression was associated with poor overall survival in lower-grade glioma (LGG). In addition, YTHDF2 expression positively correlated with expression of several immune cell markers, including PD-1, TIM-3, and CTLA-4, as well as tumor-associated macrophage gene markers, and isocitrate dehydrogenase 1 in LGG. These findings suggest that YTHDF2 is a potential prognostic biomarker that correlates with LGG tumor-infiltrating immune cells.

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Section: Discussionmentioning

confidence: 99%

YTHDF2 correlates with tumor immune infiltrates in lower-grade glioma

Lin

Wang²,

Yang³

et al. 2020

Aging

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“…Rationale for clinical trials of immune checkpoint blockade for newly diagnosed and recurrent glioblastoma is provided by results of preclinical studies ( 41 ). Furthermore, the concept of combination therapy involving with vaccine and immune checkpoint inhibitors is a promising strategy for treatment of patients with glioblastoma ( 42 ). An open-label pilot study will assess the safety, feasibility, and immunogenicity of a personalized neoantigen-based vaccine for enhancing CTL response again tumor cells plus adjuvant poly-ICLC combined with immune checkpoint inhibitors in patients with newly diagnosed, unmethylated glioblastoma (ClinicalTrials.gov Identifier: NCT03422094).…”

Section: Immune Therapymentioning

confidence: 99%

A Critical Overview of Targeted Therapies for Glioblastoma

2018

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Over the past century, treatment of malignant tumors of the brain has remained a challenge. Refinements in neurosurgical techniques, discovery of powerful chemotherapeutic agents, advances in radiotherapy, applications of biotechnology, and improvements in methods of targeted delivery have led to some extension of length of survival of glioblastoma patients. Refinements in surgery are mentioned because most of the patients with glioblastoma undergo surgery and many of the other innovative therapies are combined with surgery. However, cure of glioblastoma has remained elusive because it requires complete destruction of the tumor. Radical surgical ablation is not possible in the brain and even a small residual tumor leads to rapid recurrence that eventually kills the patient. Blood-brain barrier (BBB) comprising brain endothelial cells lining the cerebral microvasculature, limits delivery of drugs to the brain. Even though opening of the BBB in tumor core occurs locally, BBB limits systemic chemotherapy especially at the tumor periphery, where tumor cells invade normal brain structure comprising intact BBB. Comprehensive approaches are necessary to gain maximally from promising targeted therapies. Common methods used for critical evaluation of targeted therapies for glioblastoma include: (1) novel methods for targeted delivery of chemotherapy; (2) strategies for delivery through BBB and blood-tumor barriers; (3) innovations in radiotherapy for selective destruction of tumor; (4) techniques for local destruction of tumor; (5) tumor growth inhibitors; (6) immunotherapy; and (7) cell/gene therapies. Suggestions for improvements in glioblastoma therapy include: (1) controlled targeted delivery of anticancer therapy to glioblastoma through the BBB using nanoparticles and monoclonal antibodies; (2) direct introduction of genetically modified bacteria that selectively destroy cancer cells but spare the normal brain into the remaining tumor after resection; (3) use of better animal models for preclinical testing; and (4) personalized/precision medicine approaches to therapy in clinical trials and translation into practice of neurosurgery and neurooncology. Advances in these techniques suggest optimism for the future management of glioblastoma.

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“…Another report on GBM antitumor therapy compared autologous formalin-fixed tumor vaccine (AFTV), manufactured from autologous formalin-fixed tumor tissue [ 64 ], a vaccine with RT [ 67 ] and TMZ concomitant with RT standard therapy [ 68 ]. In the most recent phase IIa clinical trial, the median OS was 22.2 months and the 3-year survival rate was 38% [ 68 , 69 ]. The number of TILs was increased in recurrent tumor tissues after AFTV therapy compared with initial tumor tissue and the number of Ki-67-positive tumor cells tended to be decreased [ 70 ].…”

Section: Gbm Immunotherapy and Microenvironmental Changes After Rementioning

confidence: 99%

Therapeutic Strategies for Overcoming Immunotherapy Resistance Mediated by Immunosuppressive Factors of the Glioblastoma Microenvironment

Miyazaki

Ishikawa

Sugii

et al. 2020

Cancers

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Various mechanisms of treatment resistance have been reported for glioblastoma (GBM) and other tumors. Resistance to immunotherapy in GBM patients may be caused by acquisition of immunosuppressive ability by tumor cells and an altered tumor microenvironment. Although novel strategies using an immune-checkpoint inhibitor (ICI), such as anti-programmed cell death-1 antibody, have been clinically proven to be effective in many types of malignant tumors, such strategies may be insufficient to prevent regrowth in recurrent GBM. The main cause of GBM recurrence may be the existence of an immunosuppressive tumor microenvironment involving immunosuppressive cytokines, extracellular vesicles, chemokines produced by glioma and glioma-initiating cells, immunosuppressive cells, etc. Among these, recent research has paid attention to various immunosuppressive cells—including M2-type macrophages and myeloid-derived suppressor cells—that cause immunosuppression in GBM microenvironments. Here, we review the epidemiological features, tumor immune microenvironment, and associations between the expression of immune checkpoint molecules and the prognosis of GBM. We also reviewed various ongoing or future immunotherapies for GBM. Various strategies, such as a combination of ICI therapies, might overcome these immunosuppressive mechanisms in the GBM microenvironment.

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Prospect of Immunotherapy for Glioblastoma: Tumor Vaccine, Immune Checkpoint Inhibitors and Combination Therapy

Cited by 17 publications

References 73 publications

YTHDF2 correlates with tumor immune infiltrates in lower-grade glioma

YTHDF2 correlates with tumor immune infiltrates in lower-grade glioma

A Critical Overview of Targeted Therapies for Glioblastoma

Therapeutic Strategies for Overcoming Immunotherapy Resistance Mediated by Immunosuppressive Factors of the Glioblastoma Microenvironment

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