| First Author | Gate D | Year | 2014 |
| Journal | Proc Natl Acad Sci U S A | Volume | 111 |
| Issue | 33 | Pages | E3458-66 |
| PubMed ID | 25082897 | Mgi Jnum | J:213930 |
| Mgi Id | MGI:5586912 | Doi | 10.1073/pnas.1412489111 |
| Citation | Gate D, et al. (2014) T-cell TGF-beta signaling abrogation restricts medulloblastoma progression. Proc Natl Acad Sci U S A 111(33):E3458-66 |
| abstractText | Cancer cell secretion of TGF-beta 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-beta signaling blockade on progression of medulloblastoma (MB), the most common pediatric brain tumor. Genetic abrogation of T-cell TGF-beta 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-beta signaling blockade licenses the T-cell repertoire to kill pediatric brain tumor cells. |
