Unveiling the role of T cell dysfunction in the development and progression of glioblastoma

 

Despite the success of immunotherapy against several malignancies including melanoma and lung adenocarcinoma, glioblastoma remains the exception. CD8+ T cells are the main drivers of the response to immunotherapy, but most of them differentiate into a dysfunctional state inside the tumour. The signals underpinning CD8+ T cell dysfunction in glioblastoma remain uncharacterized. Using a transplantable mouse model of glioblastoma, we have found a high infiltration of CD4 and CD8 T cells expressing several inhibitory receptors such as PD-1, TIM-3 and LAG-3, suggesting the acquisition of a dysfunctional state. We hypothesize that chronic antigen stimulation through the T cell receptor is driving differentiation and the acquisition of a dysfunctional state on T cells, facilitating tumour progression. The main learning objectives of this talk will be to highlight the relevance of studying brain tumour immunology and to make a brief description of the approach we are using in order to identify and validate potential targets to treat this devastating disease.

 

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