6533b7d9fe1ef96bd126cf2e

RESEARCH PRODUCT

In the literature: April 2019

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Glioblastoma (GBM) remains an unmet need in Medical Oncology considering its poor prognosis and the lack of advances in therapeutics in more than one decade.1 Despite the initial enthusiasm, the development of immunotherapy in GBM has proved to be challenging, with a disappointing negative phase III clinical trial.2 Some of the phenotypic hallmarks of GBM make immunotherapy difficult. Its relatively low mutational load, its immunologically ‘cold’ microenvironment with scarce infiltrating immune effector cells, a dominant myeloid compartment composed by microglia and myeloid-derived suppressor cells and a strong immunosuppression, both local, mediated by immunosuppressive regulatory T cells and a plethora of GBM secreted cytokines, and systemic, with severe lymphopenia related with standard first-line treatment and the use of dexamethasone. Three publications in a recent issue of Nature Medicine show some steps to overcome these limitations, including a comprehensive characterisation of the immune landscape and genomics of GBM patients exposed to checkpoint inhibitors,3 as well as neoadjuvant treatment in two small trials with a strong translational research component.4 5 In the first article, leaded by investigators of the Columbia University, a retrospective series of 66 recurrent GBM patients treated with checkpoint inhibitors (nivolumab or pembrolizumab) were extensively profiled, analysing 58 whole exomes and 38 transcriptomes from longitudinal tumour-matched blood normal samples for 17 patients and incorporating the results from a cancer gene panel of 39 patients. They identified 17 long-term responders, defining response by at least one of the following two criteria: (1) tissue sampled during surgery after PD-1 therapy mostly showed only an inflammatory response and very few or no tumour cells, or (2) tumour volumes by MRI were either stable or shrinking continually over at least 6 months. Response to the PD1 inhibitors was found to be significantly associated with overall survival (OS). Median OS was …