Interferon-stimulated neutrophils as a predictor of immunotherapy response
Menée à partir d'échantillons sanguins, de modèles murins, de données publiques et d'échantillons sanguins prélevés sur des patients atteints d'un mélanome ou d'un cancer du poumon non à petites cellules, cette étude met en évidence l'intérêt des neutrophiles Ly6Ehi pour prédire la réponse tumorale à une immunothérapie
Despite the remarkable success of anti-cancer immunotherapy, its effectiveness remains confined to a subset of patients?emphasizing the importance of predictive biomarkers in clinical decision-making and further mechanistic understanding of treatment response. Current biomarkers, however, lack the power required to accurately stratify patients. Here, we identify interferon-stimulated, Mouse strainsneutrophils as a blood-borne biomarker of anti-PD1 response in mice at baseline. Ly6Ehi neutrophils are induced by tumor-intrinsic activation of the STING (stimulator of interferon genes) signaling pathway and possess the ability to directly sensitize otherwise non-responsive tumors to anti-PD1 therapy, in part through IL12b-dependent activation of cytotoxic T cells. By translating our pre-clinical findings to a cohort of patients with non-small cell lung cancer and melanoma (n = 109), and to public data (n = 1440), we demonstrate the ability of Ly6Ehi neutrophils to predict immunotherapy response in humans with high accuracy (average AUC ≈ 0.9). Overall, our study identifies a functionally active biomarker for use in both mice and humans.
Cancer Cell , article en libre accès, 2023