Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 111, Issue 33, Pages E3458-E3466Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1412489111
Keywords
cancer immunology; neuroimmunology; neuro-oncology
Categories
Funding
- National Institutes of Health (NIH) National Research Service Award [1F31NS083339-01A1]
- NIH Grants National Institute on Aging [5R00AG029726-04, 1R01NS076794-01]
- National Institute of Neurological Disorders and Stroke
- Alzheimer's Association Zenith Fellows Award [ZEN-10-174633]
- American Federation of Aging Research/Ellison Medical Foundation Julie Martin Mid-Career Award in Aging Research [M11472]
- Margaret E. Early Medical Research Trust
- California Institute for Regenerative Medicine [RM1-01735]
- Zilkha Neurogenetic Institute
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available