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Comprehensive analysis of inhibitory checkpoint ligand expression by glioblastoma cells
Author(s) -
Robilliard Laverne D,
Yu Jane,
Anchan Akshata,
Joseph Wayne,
Finlay Graeme,
Angel Catherine E,
Scott Graham E
Publication year - 2021
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1111/imcb.12428
Subject(s) - downregulation and upregulation , flow cytometry , cancer research , immunotherapy , immune checkpoint , glioblastoma , immune system , cytotoxic t cell , biology , cell , glioma , immunology , in vitro , biochemistry , gene , genetics
Glioblastoma is a highly aggressive brain malignancy commonly refractory to classical and novel chemo‐, radio‐ and immunotherapies, with median survival times of ~15 months following diagnosis. Poor immunological responses exemplified by the downregulation of T‐cell activity, and upregulation of immunosuppressive cells within the tumor microenvironment have limited the effectiveness of immunotherapy in glioblastoma to date. Here we show that glioblastoma cells express a large repertoire of inhibitory checkpoint ligands known to control effector T cell responses. Furthermore, flow cytometry analysis reveals that glioblastoma cells with an enhanced stem cell‐like phenotype express several investigated ligands at significant levels on their cell surface. This reveals that glioblastoma stem‐like cells express suppressive ligands with the potential of suppressing major T cell checkpoint receptors. With this information, it is now essential that we understand the relevance of this extensive repertoire of immune checkpoint ligands and their functional consequence on immune evasion in glioblastoma. This is necessary to develop effective immunotherapeutics and to be able to match treatment to patient, especially in the light of CheckMate 143.