T-cell TGF-β signaling abrogation restricts medulloblastoma progression

Proc Natl Acad Sci U S A. 2014 Aug 19;111(33):E3458-66. doi: 10.1073/pnas.1412489111. Epub 2014 Jul 31.


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.

Keywords: cancer immunology; neuro-oncology; neuroimmunology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / metabolism*
  • Cell Differentiation
  • Flow Cytometry
  • Mice
  • Mice, Inbred C57BL
  • Signal Transduction*
  • Transforming Growth Factor beta / metabolism*


  • Transforming Growth Factor beta