Journal
CELL REPORTS
Volume 6, Issue 6, Pages 992-999Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2014.02.016
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Funding
- National Cancer Institute of the National Institutes of Health [R01CA122976, U54CA163117, R01CA146092, P30CA033572]
- Tim Nesviq Fund at City of Hope Comprehensive Cancer Center
- HEADstrong Foundation
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S1PR1 signaling has been shown to restrain the number and function of regulatory T (Treg) cells in the periphery under physiological conditions and in colitis models, but its role in regulating tumor-associated T cells is unknown. Here, we show that S1PR1 signaling in T cells drives Treg accumulation in tumors, limits CD8(+) T cell recruitment and activation, and promotes tumor growth. T-cell-intrinsic S1PR1 affects Treg cells, but not CD8(+) T cells, as demonstrated by adoptive transfer models and transient pharmacological S1PR1 modulation. An increase in S1PR1 in CD4(+) T cells promotes STAT3 activation and JAK/STAT3-dependent Treg tumor migration, whereas STAT3 ablation in T cells diminishes tumor-associated Treg accumulation and tumor growth. Our study demonstrates a stark contrast between the consequences of S1PR1 signaling in Treg cells in the periphery versus tumors.
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