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  • T-cell TGF-β signaling abro...
    David Gate; Moise Danielpour; Javier Rodriguez, Jr; Gi-Bum Kim; Rachelle Levy; Serguei Bannykh; Joshua J. Breunig; Susan M. Kaech; Richard A. Flavell; Terrence Town

    Proceedings of the National Academy of Sciences - PNAS, 08/2014, Letnik: 111, Številka: 33
    Journal Article

    Cancer cell secretion of TGF-β is a potent mechanism for immune evasion. However, little is known about how central nervous system tumors guard against immune eradication. We sought to determine the impact of T-cell TGF-β signaling blockade on progression of medulloblastoma (MB), the most common pediatric brain tumor. Genetic abrogation of T-cell TGF-β signaling mitigated tumor progression in the smoothened A1 (SmoA1) transgenic MB mouse. T regulatory cells were nearly abolished and antitumor immunity was mediated by CD8 cytotoxic T lymphocytes. To define the CD8 T-cell subpopulation responsible, primed CD8 T cells were adoptively transferred into tumor-bearing immunocompromised SmoA1 recipients. This led to generation of CD8 ⁺/killer cell lectin-like receptor G1 high (KLRG1 ʰⁱ)/IL-7R ˡᵒ short-lived effector cells that expressed granzyme B at the tumor. These results identify a cellular immune mechanism whereby TGF-β signaling blockade licenses the T-cell repertoire to kill pediatric brain tumor cells.