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Expression of inhibitory checkpoint ligands by Glioblastoma Multiforme cells and the implications of an enhanced stem cell-like phenotype

Robilliard, L. D.; Joseph, W.; Finlay, G.; Angel, C. E.; Graham, S.

2019-12-20 cell biology
10.1101/2019.12.19.883397 bioRxiv
Show abstract

Glioblastoma Multiforme is a highly aggressive brain malignancy commonly refractory to classical and novel chemo-, radio- and immuno-therapies, with median survival times of ~15 months following diagnosis. Poor immunological responses exemplified by the down-regulation of T-cell activity, and upregulation of immunosuppressive cells within the tumour micro-environment have limited the effectiveness of immunotherapy in GBM to date. Here we show that GBM cells express a large repertoire of inhibitory checkpoint ligands. Furthermore, GBM cells with an enhanced stem cell-like phenotype exhibit heightened levels of inhibitory checkpoint ligands, compared to non-stem cell-like GBM cells. Understanding how GBM modulates an extensive repertoire of immune checkpoint ligands and the functional consequence on immune evasion are necessary to develop effective immuno-therapeutics.

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