A review of glioblastoma immunotherapy
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TOPIC REVIEW
A review of glioblastoma immunotherapy Ravi Medikonda1 · Gavin Dunn2 · Maryam Rahman3 · Peter Fecci4 · Michael Lim1 Received: 28 January 2020 / Accepted: 28 February 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Introduction Glioblastoma is a very aggressive cancer with dismal prognosis despite standard of care including surgical resection, radiation therapy, and chemotherapy. There is interest in applying immunotherapy to glioblastoma as this modality has demonstrated remarkable improvements in the management of several solid tumors including melanoma, renal cell carcinoma, and non-small cell lung cancer. This review aims to provide an overview of the current state of glioblastoma immunotherapy. Methods Literature search was performed on PubMed between 1961 and 2020. Results Initial clinical trials of checkpoint inhibitors and vaccine therapy for glioblastoma have largely been disappointing for both primary and recurrent glioblastoma. This failure has been attributed to glioblastoma’s highly immunosuppressive environment and multiple mechanisms of therapy resistance including high tumor heterogeneity, low mutational burden, systemic immunosuppression, and local immune dysfunction. Conclusions Current clinical trials are exploring combination therapy and novel treatment strategies beyond immune checkpoint therapies and vaccine therapy such as CAR T cells. There is also an effort to establish synergy between immunotherapy and current standard of care. Furthermore, recent advances in personalized neoantigen vaccines suggest a shift towards personalized, patient-specific GBM treatment. Keywords Glioblastoma · Immunotherapy · GBM Immunotherapy
The promise of immunotherapy The field of cancer immunotherapy arose from the concept of cancer immunosurveillance, first conceived by William Coley in the 1890 s, followed by Ehrlich, and then Thomas and Burnet in the 1950s and 1960s [1–4]. Cancer immunosurveillance is the notion that the immune system can actively detect and eliminate tumor cells. However, some tumor cells do survive and develop the ability to evade the * Michael Lim [email protected] 1
Department of Neurosurgery, The Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Phipps 123, Baltimore, MD 21287, USA
2
Department of Neurosurgery, Washington University School of Medicine in St. Louis, St. Louis, MO, USA
3
Department of Neurosurgery, University of Florida, Gainesville, FL, USA
4
Department of Neurosurgery, Duke University Hospital, Durham, NC, USA
immune system through a process of immunoediting [5]. Cancer immunotherapy aims to overcome the immunoresistance of tumor cells to promote tumor eradication. This strategy has shown great promise in recent years especially since the development of immune checkpoint inhibitors (ICIs) [6]. Immune checkpoints are an intrinsic feature of the immune system designed to maintain self-tolerance [7]. Cancer cells can exploit this feature by upregulating immune checkpoint pathways such as p
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