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

Autor:	Huff WX; Department of Neurosurgery, Indiana University Simon Cancer Center, Indiana University School of Medicine, Indiana, IN., Bam M; Department of Neurosurgery, University of Wisconsin School of Medicine and Public Health, Madison, WI; and., Shireman JM; Department of Neurosurgery, University of Wisconsin School of Medicine and Public Health, Madison, WI; and., Kwon JH; Department of Neurosurgery, Indiana University Simon Cancer Center, Indiana University School of Medicine, Indiana, IN., Song L; Department of Neurosurgery, Indiana University Simon Cancer Center, Indiana University School of Medicine, Indiana, IN., Newman S; Department of Neurosurgery, Indiana University Simon Cancer Center, Indiana University School of Medicine, Indiana, IN., Cohen-Gadol AA; Department of Neurosurgery, Indiana University Simon Cancer Center, Indiana University School of Medicine, Indiana, IN., Shapiro S; Department of Neurosurgery, Indiana University Simon Cancer Center, Indiana University School of Medicine, Indiana, IN., Jones T; Department of Medical and Molecular Genetics, Indiana University Simon Cancer Center, Indiana University School of Medicine, Indiana, IN., Fulton K; Department of Medical and Molecular Genetics, Indiana University Simon Cancer Center, Indiana University School of Medicine, Indiana, IN., Liu S; Department of Medical and Molecular Genetics, Indiana University Simon Cancer Center, Indiana University School of Medicine, Indiana, IN., Tanaka H; Department of Medical and Molecular Genetics, Indiana University Simon Cancer Center, Indiana University School of Medicine, Indiana, IN., Liu Y; Department of Medical and Molecular Genetics, Indiana University Simon Cancer Center, Indiana University School of Medicine, Indiana, IN., Wan J; Department of Medical and Molecular Genetics, Indiana University Simon Cancer Center, Indiana University School of Medicine, Indiana, IN., Dey M; Department of Neurosurgery, University of Wisconsin School of Medicine and Public Health, Madison, WI; and dey@neurosurgery.wisc.edu.
Jazyk:	angličtina
Zdroj:	ImmunoHorizons [Immunohorizons] 2021 Jun 08; Vol. 5 (6), pp. 395-409. Date of Electronic Publication: 2021 Jun 08.
DOI:	10.4049/immunohorizons.2100008
Abstrakt:	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 and/or function of these CD8 + CD28 - T cells is unknown. In this clinical correlative study, we investigated the effect of aging as well as tumor microenvironment on CD8 + T cell phenotype as an indicator of its function in GBM patients. We systematically analyzed and describe a large population of CD8 + CD28 - T cells in both the blood and tumor-infiltrating lymphocytes of GBM patients. We found that phenotypically these CD8 + CD28 - T cells represent a distinct population compared with exhausted T cells. Comparative transcriptomic and pathway analysis of CD8 + CD28 - T cell populations in GBM patients revealed that tumor microenvironment might be influencing several immune related pathways and thus further exaggerating the age associated immune dysfunction in this patient population. (Copyright © 2021 The Authors.)
Databáze:	MEDLINE
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