Na, K-ATPase alpha
Menée à l'aide de lignées cellulaires, de modèles murins ainsi que d'échantillons sanguins et d'échantillons tissulaires prélevés sur des patients atteints d'un cancer du poumon non à petites cellules, cette étude met en évidence un mécanisme par lequel l'ATPase alpha1 dépendante du calcium et du potassium, en interagissant avec l'ouabaïne endogène (une hormone adrénergique), modifie le microenvironnement et favorise l'échappement immunitaire
Dysregulated endocrine hormones (EHs) contribute to tumorigenesis, but how EHs affect the tumor immune microenvironment (TIM) and the immunotherapy of non–small cell lung cancer (NSCLC) is still unclear. Here, endogenous ouabain (EO), an adrenergic hormone, is elevated in patients with NSCLC and closely related to tumor pathological stage, metastasis, and survival. EO promotes the suppression of TIM in vivo by modulating the expression of immune checkpoint proteins, in which programmed cell death protein ligand 1 (PD-L1) plays a major role. EO increases PD-L1 transcription; however, the EO receptor Na- and K-dependent adenosine triphosphatase (Na, K-ATPase) α1 interacts with PD-L1 to trigger the endocytic degradation of PD-L1. This seemingly contradictory result led us to discover the mechanism whereby EO cooperates with Na, K-ATPase α1 to finely control PD-L1 expression and dampen tumoral immunity. In conclusion, the Na, K-ATPase α1/EO signaling facilitates immune escape in lung cancer, and manipulation of this signaling shows great promise in improving immunotherapy for lung adenocarcinoma. The Na, K-ATPase α1/EO signaling in lung adenocarcinoma facilitates tumor immune escape by fine-tuning PD-L1 expression.
Science Advances 2023