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Cell Rep. 2014 Mar 27;6(6):992-999. doi: 10.1016/j.celrep.2014.02.016. Epub 2014 Mar 13.

S1PR1 is crucial for accumulation of regulatory T cells in tumors via STAT3.

Author information

1
Department of Cancer Immunotherapeutics and Tumor Immunology, Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA.
2
Department of Immunology, Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA.
3
Department of Cancer Immunotherapeutics and Tumor Immunology, Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA. Electronic address: hyu@coh.org.

Abstract

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.

PMID:
24630990
PMCID:
PMC3988983
DOI:
10.1016/j.celrep.2014.02.016
[Indexed for MEDLINE]
Free PMC Article

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