What question did this study set out to answer?

The research aims to investigate the role of ENPP3 in ccRCC progression and its potential as a therapeutic target.

February 22, 2026Open Access

ENPP3 drives ccRCC progression by cGAMP hydrolysis and STING–IFN suppression

Key Points

The research aims to investigate the role of ENPP3 in ccRCC progression and its potential as a therapeutic target.
Analyzed the function of ENPP3 in ccRCC cells under hypoxic conditions.
Examined the effects of ENPP3 inhibition on STING-dependent immune responses.
Investigated cGAMP hydrolysis as a mechanism of ENPP3's action.
Inhibition of ENPP3 reactivated STING pathways, enhancing anti-tumor immunity.
cGAMP levels increased following ENPP3 inhibition, indicating a disruption in its hydrolysis.
Hypoxia enhances ENPP3 expression, correlating with ccRCC progression.

Abstract

ENPP3 is a hypoxia-driven, cGAMP-targeting innate immune checkpoint in ccRCC. Its inhibition reactivates STING-dependent anti-tumor immunity, providing a strong preclinical rationale for targeting ENPP3 therapeutically.

ENPP3 drives ccRCC progression by cGAMP hydrolysis and STING–IFN suppression

Key Points

Abstract

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