C-type lectin receptor Dectin-1 blockade on tumour-associated macrophages improves anti-PD-1 efficacy in gastric cancer
Menée en Chine à partir d'échantillons tumoraux et d'échantillons tissulaires adjacents fixés au formaldéhyde et inclus en paraffine après prélèvement sur 496 patients atteints d'un cancer gastrique, cette étude met en évidence l'intérêt de bloquer la dectine-1 (une lectine de type C) des macrophages associés à la tumeur pour améliorer l'efficacité antitumorale des anti-PD1
Background : This study aimed to investigate the expression and clinical significance of Dendritic cell-associated C-type lectin-1 (Dectin-1) in gastric cancer (GC), and to explore the mechanism of Dectin-1 regulating tumour-associated macrophage (TAM)-mediated immune evasion in GC. Methods : The association of Dectin-1+ cells with clinical outcomes was inspected by immunohistochemistry on tumour microarrays. Flow cytometry and RNA sequencing were applied to detect characteristics of T cells, phenotypic and transcriptional features of Dectin-1+ TAMs. The effect of Dectin-1 blockade was evaluated using an in vitro intervention experiment based on fresh GC tissues. Results : High infiltration of intratumoral Dectin-1+ cells predicted poor prognosis in GC patients. Dectin-1+ cells were mainly composed of TAMs, and the accumulation of Dectin-1+ TAMs was associated with T-cell dysfunction. Notably, Dectin-1+ TAMs exhibited an immunosuppressive phenotype. Furthermore, blockade of Dectin-1 could reprogramme Dectin-1+ TAMs and reactivate anti-tumour effects of T cells, as well as enhanced PD-1 inhibitor-mediated cytotoxicity of CD8+ T cells against tumour cells. Conclusions : Dectin-1 could affect T-cell anti-tumour immune response by regulating the immunosuppressive function of TAMs, leading to poor prognosis and immune evasion in GC patients. Blockade of Dectin-1 can be used alone or in combination with current therapeutic strategies in GC.