Challenges and opportunities in academic neurosurgery.

Clinical academia aims to bridge the gap between clinicians and scientists, by combining academic activity with clinical practice. The term 'clinical academics' generally refers to clinicians who have protected time within their job plans for undertaking academic activities. Engagement with academic activity by trainees is not only essential to fulfil necessary curriculum competencies, but also allows them to explore areas of interest outside of clinical practice and develop advanced academic skills. This article provides an overview of different routes into academic neurosurgery, and discusses the advantages and difficulties in pursuing this career path. It also covers the differences between postgraduate research degrees and explores the different job plan models available at consultant level. Academic neurosurgery is a rewarding career and opportunities should be made available to those who wish to explore it further. Developing academic careers may have a positive impact on wider workforce planning strategies and improve the delivery of high-quality evidence-based neurosurgical care.

Expression profiling of single cells and patient cohorts identifies multiple immunosuppressive pathways and an altered NK cell phenotype in glioblastoma.

Glioblastoma (GBM) is an aggressive cancer with a very poor prognosis. Generally viewed as weakly immunogenic, GBM responds poorly to current immunotherapies. To understand this problem more clearly we used a combination of natural killer (NK) cell functional assays together with gene and protein expression profiling to define the NK cell response to GBM and explore immunosuppression in the GBM microenvironment. In addition, we used transcriptome data from patient cohorts to classify GBM according to immunological profiles. We show that glioma stem-like cells, a source of post-treatment tumour recurrence, express multiple immunomodulatory cell surface molecules and are targeted in preference to normal neural progenitor cells by natural killer (NK) cells ex vivo. In contrast, GBM-infiltrating NK cells express reduced levels of activation receptors within the tumour microenvironment, with hallmarks of transforming growth factor (TGF)-ß-mediated inhibition. This NK cell inhibition is accompanied by expression of multiple immune checkpoint molecules on T cells. Single-cell transcriptomics demonstrated that both tumour and haematopoietic-derived cells in GBM express multiple, diverse mediators of immune evasion. Despite this, immunome analysis across a patient cohort identifies a spectrum of immunological activity in GBM, with active immunity marked by co-expression of immune effector molecules and feedback inhibitory mechanisms. Our data show that GBM is recognized by the immune system but that anti-tumour immunity is restrained by multiple immunosuppressive pathways, some of which operate in the healthy brain. The presence of immune activity in a subset of patients suggests that these patients will more probably benefit from combination immunotherapies directed against multiple immunosuppressive pathways.