Sex-differences in GBM explored and extra circular DNA in medulloblastoma

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Sex-Biased T-cell Exhaustion Drives Differential Immune Responses in Glioblastoma. Differences in incidence and outcomes for men and women with glioblastoma (GBM) are well recognised, with emerging evidence suggesting that these extend to genetic/epigenetic and cellular differences, including immune responses. However, the mechanisms behind immunologic sex differences are not fully understood.  

Using mouse models, the researchers in this study concluded that sex-biased pre-determined behaviour of T cells (immune cells) is critical for inducing the differences in GBM progression and immunotherapy response between the sexes, and suggest that sex-specific approaches can be leveraged to potentially improve the therapeutic efficacy of immunotherapy in GBM. Published in AACR.  

TIM-3 blockade in diffuse intrinsic pontine glioma models promotes tumour regression and antitumour immune memory. In this study, researchers have demonstrated that the immune checkpoint TIM-3 (HAVCR2) is highly expressed in both tumour cells and microenvironmental cells, mainly microglia and macrophages, in diffuse intrinsic pontine glioma (DIPG). They go on to show that inhibition of TIM-3 in models of DIPG prolongs survival and produces long-term survivors free of disease that harbour immune memory.  

Published in Cancer Cell, they explain that this antitumour effect is driven by the direct effect of TIM-3 inhibition in tumour cells, the coordinated action of several immune cell populations, and the secretion of chemokines/cytokines that create a proinflammatory tumour microenvironment favouring a potent antitumour immune response. 

Circular extrachromosomal DNA promotes tumour heterogeneity in high-risk medulloblastoma. Circular extrachromosomal DNA (ecDNA) in patient tumours is an important driver of oncogenic gene expression, evolution of drug resistance and poor patient outcomes. Applying computational methods for the detection and reconstruction of ecDNA across a retrospective cohort of 481 medulloblastoma tumours from 465 patients, researchers identified circular ecDNA in 82 patients (18%). Patients with ecDNA-positive medulloblastoma were more than twice as likely to relapse and three times as likely to die within 5 years of diagnosis. Published in Nature Genetics. 


New NIHR Research Delivery Network created. The network will play a critical and active role in supporting the health and care research system to bring innovative new treatments and care to patients, carers and the public. 

The new National Institute for Health and Care Research - Research Delivery Network (NIHR RDN) will commence in 2024 to support the successful delivery of health and social care research in England. It will take over from NIHR - Clinical Research Network (NIHR CRN). 

The Department of Health and Social Care (DHSC) has designated the University of Leeds as the single host of the new NIHR RDN Co-ordinating Centre (RDNCC) from 1 April 2024. This contract has been awarded following a commercial procurement exercise.  Read more here. 

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