CNS cancer immunity cycle and strategies to target this for glioblastoma

Malaka Ameratunga, Niamh Coleman, Liam Welsh, Frank Saran and Juanita Lopez _

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Oncotarget. 2018; 9:22802-22816. https://doi.org/10.18632/oncotarget.24896

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Malaka Ameratunga1, Niamh Coleman1, Liam Welsh2, Frank Saran2 and Juanita Lopez1

1Drug Development Unit, Royal Marsden Hospital and The Institute of Cancer Research, Sutton SM2 5PT, UK

2Department of Neuro-Oncology, Royal Marsden Hospital and The Institute of Cancer Research, Sutton SM2 5PT, UK

Correspondence to:

Juanita Lopez, email: [email protected]

Keywords: glioblastoma; immunotherapy; cancer-immunity cycle; checkpoint inhibitors; clinical trials

Received: November 30, 2017    Accepted: March 11, 2018    Published: April 27, 2018


Immunotherapeutics have revolutionized the management of solid malignancies over the last few years. Nevertheless, despite relative successes of checkpoint inhibitors in numerous solid tumour types, success in tumours of the central nervous system (CNS) has been lacking. There are several possible reasons for the relative lack of success of immunotherapeutics in this setting, including the immune microenvironment of glioblastoma, lymphocyte tracking through the blood-brain barrier (BBB) into the central nervous system and impairment of drug delivery into the CNS through the BBB. This review utilizes the cancer-immunity cycle as a conceptual framework through which the specific challenges associated with the development of immunotherapeutics for CNS malignancies can be viewed.

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