What question did this study set out to answer?

This research aims to explore how extracellular ATP and P2RY2 signaling influence immunotherapy resistance in solid tumors.

July 4, 2026ImmunityOpen Access

Extracellular ATP-P2RY2 signaling drives intratumoral prostaglandin E2 accumulation and adaptive resistance to immunotherapy in solid tumors

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Randomized trial uncovers how ATP-P2RY2 signaling affects immune response in solid tumors, suggesting potential therapeutic targets.

This research aims to explore how extracellular ATP and P2RY2 signaling influence immunotherapy resistance in solid tumors.
Investigated extracellular ATP concentrations in the tumor microenvironment during immunotherapy.
Examined the effects of genetic deletion and pharmacologic inhibition of P2RY2 on prostaglandin E2 accumulation.
Utilized P2RY2 antagonist monoclonal antibodies to assess therapeutic efficacy in vivo and ex vivo.
P2RY2 blockade reduced baseline intratumoral prostaglandin E2 (PGE₂) levels and prevented therapy-induced PGE₂ accumulation.
Altered the immune cell composition in the tumor microenvironment, enhancing T cell responses.
Overcame resistance to immune checkpoint blockade, CAR-T, and TCR-T therapies, showing a significant therapeutic benefit.

Hu et al. (2026) studied this question.

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