CNS cancer immunity cycle and strategies to target this for glioblastoma.

// Malaka Ameratunga 1 , Niamh Coleman 1 , Liam Welsh 2 , Frank Saran 2 and Juanita Lopez 1 1 Drug Development Unit, Royal Marsden Hospital and The Institute of Cancer Research, Sutton SM2 5PT, UK 2 Department of Neuro-Oncology, Royal Marsden Hospital and The Institute of Cancer Research, Sutton SM2 5PT, UK Correspondence to: Juanita Lopez, email: juanita.lopez@icr.ac.uk Keywords: glioblastoma; immunotherapy; cancer-immunity cycle; checkpoint inhibitors; clinical trials Received: November 30, 2017     Accepted: March 11, 2018     Published: April 27, 2018 ABSTRACT 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.