Cited by 34Glioma Diagnosis and TreatmentCancer Immunotherapy and BiomarkersImmunotherapy and Immune Responses

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Immunotherapy Resistance in Glioblastoma

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Wang, Elaina J., Chen, Jia-Shu, Jain, Saket, Morshed, Ramin A., Haddad, Alexander F., Gill, Sabraj, Beniwal, Angad S., Aghi, Manish K.·2021·Frontiers in Genetics

DOI 10.3389/fgene.2021.750675PMC PMC8718605

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Abstract

Glioblastoma is the most common malignant primary brain tumor in adults. Despite treatment consisting of surgical resection followed by radiotherapy and adjuvant chemotherapy, survival remains poor at a rate of 26.5% at 2 years. Recent successes in using immunotherapies to treat a number of solid and hematologic cancers have led to a growing interest in harnessing the immune system to target glioblastoma. Several studies have examined the efficacy of various immunotherapies, including checkpoint inhibitors, vaccines, adoptive transfer of lymphocytes, and oncolytic virotherapy in both pre-clinical and clinical settings. However, these therapies have yielded mixed results at best when applied to glioblastoma. While the initial failures of immunotherapy were thought to reflect the immunoprivileged environment of the brain, more recent studies have revealed immune escape mechanisms created by the tumor itself and adaptive resistance acquired in response to therapy. Several of these resistance mechanisms hijack key signaling pathways within the immune system to create a protumoral microenvironment. In this review, we discuss immunotherapies that have been trialed in glioblastoma, mechanisms of tumor resistance, and strategies to sensitize these tumors to immunotherapies. Insights gained from the studies summarized here may help pave the way for novel therapies to overcome barriers that have thus far limited the success of immunotherapy in glioblastoma.

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Md Yy, 2021, The Safety and Efficacy Study of Autologous Tumor-Infiltrating T LymphocyteTILnd Transgenic Modified TIL Cells Adoptive Therapies for Patients with Glioblastoma Multiforme
MediciNova, 2021, Phase 1b/2a Single-Center, Open-Label, Dose Escalation Study to Evaluate the Safety, Tolerability, and Efficacy of MN-166 (Ibudilast) and Temozolomide Combination Treatment in Patients with Newly Diagnosed or Recurrent Glioblastoma
National Cancer Institute Nci, 2021, A Safety Run-In and Phase II Study Evaluating the Efficacy, Safety, and Impact on the Tumor Microenvironment of the Combination of Tocilizumab, Atezolizumab, and Fractionated Stereotactic Radiotherapy in Recurrent Glioblastoma
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Authors: Wang, E. J., Chen, J.-S., Jain, S., Morshed, R. A., Haddad, A. F., Gill, S., Beniwal, A. S., & Aghi, M. K.
Affiliations: Brown University (US)
University of California, San Francisco (US)
Corresponding author: Aghi, Manish K.
ORCID: Wang, Elaina J.
Chen, Jia-Shu
Jain, Saket
Morshed, Ramin A.
Haddad, Alexander F.
Beniwal, Angad S.
Aghi, Manish K.
Venue: Frontiers in Genetics
Publisher: Frontiers Media SA
Published: 2021-12-17
Volume: 12
Pages: 750675-750675
ISSN: 1664-8021 (ISSN-L)
DOI: 10.3389/fgene.2021.750675
PMC: PMC8718605
OpenAlex: W4200562336
Cited by: 34
References: 269
Citations by year: 2026: 5 · 2025: 7 · 2024: 8 · 2023: 12 · 2022: 2
FWCI: 0.78
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
Locations: Frontiers in Genetics (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
eScholarship (California Digital Library) (submittedVersion, cc-by)
Funders: National Cancer Institute (R01CA227136)
National Institute of Neurological Disorders and Stroke (R01NS079697)
Topics: Health Sciences › Medicine › Oncology › Glioma Diagnosis and Treatment
Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords: glioblastoma, immunotherapy resistance, immune checkpoint inhibitors, cancer vaccines, adoptive immunotherapy, oncolytic virotherapy, tumor immune evasion, tumor microenvironment, immune privilege, adaptive resistance, radiosensitization

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Immunotherapy Resistance in Glioblastoma

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