S1PR1 Is Crucial for Accumulation of Regulatory T Cells in Tumors via STAT3

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.

Abstract licence: CC BY-NC

31 more references, whose wording the paper’s licence keeps private.

• STAT3 pathway in cancers: Past, present, and future · 2022

• Study and analysis of antitumor resistance mechanism of PD1/PD‐L1 immune checkpoint blocker · 2020

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• T Regulatory Cells and Priming the Suppressive Tumor Microenvironment · 2019

• Metabolic Pathways Involved in Regulatory T Cell Functionality · 2019

• Regulatory T Cells in the Tumor Microenvironment and Cancer Progression: Role and Therapeutic Targeting · 2016

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  Sphingosine-1-Phosphate Signaling in Immune Cells and Inflammation: Roles and Therapeutic Potential · 2016

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