Clinical significance of combined tumour-infiltrating lymphocytes and microsatellite instability status in colorectal cancer: a systematic review and network meta-analysis
A partir d'une revue systématique de la littérature publiée entre 1990 et 2024 (21 études, 14 028 patients), cette méta-analyse examine le rôle de la signalisation PD-L1 des cellules tumorales dans la transition épithélio-mésenchymateuse des cancers du poumon non à petites cellules (NSCLC) puis évalue l'association entre cette transition épithélio-mésenchymateuse et la survie après traitement par inhibiteur de point de contrôle immunitaire d'un NSCLC exprimant fortement PD-L1
Background : We investigated the role of tumor cell-intrinsic PD-L1 signaling in the epithelial−mesenchymal transition (EMT) in non-small-cell lung cancer (NSCLC) and the role of EMT as a predictive biomarker for immune checkpoint inhibitor (ICI) therapy.
Methods : PD-L1-overexpressing or PD-L1-knockdown NSCLC cells underwent RNA-seq and EMT phenotype assessment. Mouse lung cancer LLC cells were injected into nude mice. Two cohorts of patients with NSCLC undergoing ICI therapy were analyzed.
Results : RNA-seq showed that EMT pathways were enriched in PD-L1-high NSCLC cells. EMT was enhanced by PD-L1 in NSCLC cells, which was mediated by transforming growth factor-
β (TGFβ). PD-L1 promoted the activation of p38-MAPK by binding to and inhibiting the protein phosphatase PPM1B, thereby increasing the TGFβ production. Tumor growth and metastasis increased in nude mice injected with PD-L1-overexpressing LLC cells. In the ICI cohort, EMT signature was higher in patients with progressive disease than in those with responses, and EMT was significantly associated with poor survival in PD-L1-high NSCLC. In PD-L1-high NSCLC, EMT was associated with increased M2-macrophage and regulatory T-cell infiltrations and decreased cytotoxic T-cell infiltration.
Conclusions
:
Tumor cell-intrinsic PD-L1 function contributes to NSCLC progression by promoting EMT. EMT may predict an unfavorable outcome after ICI therapy in PD-L1-high NSCLC.
The Lancet Gastroenterology & Hepatology , article en libre accès, 2023