Aging- and Tumor-Mediated Increase in CD8⁺CD28^- T Cells Might Impose a Strong Barrier to Success of Immunotherapy in Glioblastoma.

ABSTRACT: Clinical use of various forms of immunotherapeutic drugs in glioblastoma (GBM), has highlighted severe T cell dysfunction such as exhaustion in GBM patients. However, reversing T cell exhaustion using immune checkpoint inhibitors in GBM clinical trials has not shown significant overall survival benefit. Phenotypically, CD8⁺ T cells with downregulated CD28 coreceptors, low CD27 expression, increased CD57 expression, and telomere shortening are classified as senescent T cells. These senescent T cells are normally seen as part of aging and also in many forms of solid cancers. Absence of CD28 on T cells leads to several functional irregularities including reduced TCR diversity, incomplete activation of T cells, and defects in Ag-induced proliferation. In the context of GBM, presence

SUBMITTER: Huff WX 

PROVIDER: S-EPMC8591704 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature