Antigen-specific CD8+CD39+ cytotoxic T cell density in the microenvironment of hepatocellular carcinoma predicts patient survival
Menée à partir d'une analyse immunohistochimique multiplex d'échantillons tumoraux issus de 100 patients atteints d'un carcinome hépatocellulaire, cette étude met en évidence une association entre la densité de lymphocytes T cytotoxiques CD8+ CD39+ dans le microenvironnement tumoral et la survie
Introduction : Tumour antigen-specific CD8+CD39+ T cells (TSTs) are crucial components of anti-tumour adaptive immunity, which in tumour microenvironment (TME) may be found at various differentiation stages, from early stem-like states to terminal stages of exhaustion. Our aim was the evaluation of TSTs quantitative and qualitative characteristics in hepatocellular carcinoma (HCC) TME, depending on whether they exhibit stem-like or exhaustion features.
Methods : We analyzed 100 HCC patients undergoing curative hepatectomy. Multiplex immunohistochemistry (CD8/CD39/TCF1, CD8/CD39/TOX) was applied on tissue microarray sections with digital imaging used to evaluate T cell infiltration in tumour center, periphery and adjacent non-neoplastic liver. Tertiary lymphoid structures (TLS) were assessed on H&E-stained slides.
Results : In HCC TME, 72% of CD8+ T cells co-express CD39, while 44% of CD8+CD39+ TSTs co-express TCF1 (stem-like) and over 50% co-express TOX (exhausted). High CD8+CD39+ T cell density in tumour periphery was linked to longer overall survival (p = 0.016). Increased CD8+CD39-TCF1+ T cell infiltration in tumour center and periphery correlated with worse prognosis (p = 0.009). TLS presence was associated with high TST density (p < 0.001).
Conclusions : Patients with HCC and high CD8+CD39+ TSTs density exhibiting a tumour-reactive phenotype have improved survival, suggesting the potential role of CD8/CD39 immunohistochemistry as a prognostic tool for personalised therapeutic strategies.
British Journal of Cancer , article en libre accès, 2025