Intratumoral PD-1+CD8+ T cells associate poor clinical outcomes and adjuvant chemotherapeutic benefit in gastric cancer
Menée en Chine à partir d'échantillons tumoraux prélevés sur 691 patients atteints d'un cancer gastrique, cette étude met en évidence une association entre l'abondance de lymphocytes T PD-1+CD8+ dans la tumeur, une mauvaise réponse thérapeutique à une chimiothérapie adjuvante et un pronostic défavorable
Background : Although PD-1 has been reported to be a marker of T-cell exhaustion in several malignancies, the biological role of PD-1+CD8+ T cells in gastric cancer (GC) remains unclear. Herein, we aimed to investigate the role of PD-1+CD8+ T cells in the tumour microenvironment and its clinical significance in GC.
Designs : This study included 441 tumour microarray specimens and 60 Flow cytometry specimens of GC patients from Zhongshan Hospital, and 250 GC patients from the Asian Cancer Research Group.
Results : Here, we demonstrated that PD-1+CD8+ T cells functioned as an independent adverse prognosticator in GC. In addition, an abundance of intratumoral PD-1+CD8+ T cells indicated worse chemotherapeutic responsiveness to fluorouracil in Stage III GC patients. Mechanistically, PD-1+CD8+ T cell high infiltration indicated an exhausted phenotype of global CD8+ T cells in GC tissues, which was characterised by elevated immune checkpoint expression including CTLA-4 and TIM-3, whereas decreased expression of perforin. Furthermore, PD-1+CD8+ T cell high-infiltration patients with Stage III GC held elevated activity of several therapeutic signal pathways.
Conclusions : Our study highlighted that PD-1+CD8+ T cell abundance predicts inferior prognosis in GC, and may serve as a novel predictive biomarker to guide therapeutic option.
British Journal of Cancer , article en libre accès, 2022