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Cell reports

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Tumor-intrinsic P2RY6 drives immunosuppression by enhancing PGE2 production

Published:23 July 2024 DOI: 10.1016/j.celrep.2024.114469 PMID: 38996067
Xilong Xu,?Yi Lu,?Longzhi Cao,?Yang Miao,?Yamei Li,?Yue Cui,?Ting Han

Abstract

Despite the success of anti-programmed cell death-1 (anti-PD-1) immunotherapy, many cancer patients remain unresponsive, and reliable predictive biomarkers are lacking. Here, we show that aberrant expression of the pyrimidinergic receptor P2RY6 is frequent in human cancers and causes immune evasion. In mouse syngeneic and human xenograft tumor models, ectopic expression of P2RY6 shapes an immunosuppressive tumor microenvironment (TME) to enhance tumor growth and resistance to immunotherapy, whereas deletion of P2RY6 from tumors with high P2RY6 expression inflames the TME to inhibit tumor growth. As a G protein-coupled receptor, P2RY6 activates Gq/phospholipase C-β signaling and stimulates the synthesis of prostaglandin E2, which is a key mediator of immunosuppression in the TME. In contrast to the essential role of P2RY6 in tumors, global deletion of P2ry6 from mice does not compromise viability. Our study thus?nominates P2RY6 as a precision immunotherapy target for patients with high tumor-intrinsic P2RY6 expression.

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Materials
Procduct Name CAS Molecular Formula Supplier Price
STAUROSPORINE 62996-74-1 C28H26N4O3 451 suppliers $10.00-$3200.00
STAUROSPORINE 62996-74-1 C28H26N4O3 451 suppliers $10.00-$3200.00
STAUROSPORINE 62996-74-1 C28H26N4O3 451 suppliers $10.00-$3200.00
STAUROSPORINE 62996-74-1 C28H26N4O3 451 suppliers $10.00-$3200.00
Uridine-5'-diphosphate disodium salt 27821-45-0 C9H15N2NaO12P2 395 suppliers $9.00-$1455.30
Uridine-5'-diphosphate disodium salt 27821-45-0 C9H15N2NaO12P2 395 suppliers $9.00-$1455.30
Uridine-5'-diphosphate disodium salt 27821-45-0 C9H15N2NaO12P2 395 suppliers $9.00-$1455.30
Uridine-5'-diphosphate disodium salt 27821-45-0 C9H15N2NaO12P2 395 suppliers $9.00-$1455.30

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