S1P-S1PR1 signaling impairs CD8 T cell metabolism and effector function in tumors.
2/5 보강
TL;DR
It is demonstrated that intratumoral CD8⁺ T cells express S1PR1, with expression predominantly enriched in the terminally exhausted subset, and Targeting the S1PR1-S1P axis or its downstream effectors offers a promising strategy to improve cancer immunotherapy outcomes.
OpenAlex 토픽 ·
Sphingolipid Metabolism and Signaling
Cancer Immunotherapy and Biomarkers
Phagocytosis and Immune Regulation
It is demonstrated that intratumoral CD8⁺ T cells express S1PR1, with expression predominantly enriched in the terminally exhausted subset, and Targeting the S1PR1-S1P axis or its downstream effectors
APA
Debashree Basak, Puspendu Ghosh, et al. (2026). S1P-S1PR1 signaling impairs CD8 T cell metabolism and effector function in tumors.. EMBO reports, 27(8), 2000-2028. https://doi.org/10.1038/s44319-026-00734-3
MLA
Debashree Basak, et al.. "S1P-S1PR1 signaling impairs CD8 T cell metabolism and effector function in tumors.." EMBO reports, vol. 27, no. 8, 2026, pp. 2000-2028.
PMID
41857410 ↗
Abstract 한글 요약
Sphingosine-1-phosphate receptor 1 (S1PR1) signaling has been linked to the regulation of immunosuppressive cell populations within the tumor microenvironment (TME); however, its role in shaping anti-tumor CD8⁺ T cell responses remains poorly defined. Herein, we demonstrate that intratumoral CD8⁺ T cells express S1PR1, with expression predominantly enriched in the terminally exhausted subset. Transcriptomic profiling, combined with pharmacological inhibition and genetic knockdown, reveals that S1PR1-S1P signaling activates the PERK (protein kinase R (PKR)-like endoplasmic reticulum kinase)-CHOP (C/EBP homologous protein) axis of the endoplasmic reticulum stress response. CHOP, in turn, upregulates transcription of Map3k13 and Map3k15, triggering downstream MAPK signaling and culminating in activation of p38MAPK. Activation of this pathway impairs CD8⁺ T cell metabolism and effector function while increasing apoptotic susceptibility. This ultimately limits the persistence and accumulation of functional CD8⁺ T cells within the TME, thereby compromising their responsiveness to anti-PD-1 therapy. Targeting the S1PR1-S1P axis or its downstream effectors offers a promising strategy to improve cancer immunotherapy outcomes.
🏷️ 키워드 / MeSH 📖 같은 키워드 OA만
- CD8-Positive T-Lymphocytes
- Sphingosine-1-Phosphate Receptors
- Animals
- Humans
- Signal Transduction
- Mice
- Tumor Microenvironment
- Neoplasms
- Lysophospholipids
- Sphingosine
- Cell Line
- Tumor
- Transcription Factor CHOP
- p38 Mitogen-Activated Protein Kinases
- Endoplasmic Reticulum Stress
- CD8+ T Cells
- ER Stress
- S1P-S1PR1
🏷️ 같은 키워드 · 무료전문 — 이 논문 MeSH/keyword 기반
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