Liver sinusoidal endothelial cells contribute to CD8 T cell tolerance to systemic circulating carcinoembryonic antigen: A new mechanism of Tumour-immune-Suppression

The observation that tumours progress in patients with colorectal carcinoma despite the presence of tumour-specific immune responses suggests that tumour development leads to a number of immune suppressive mechanisms. These mechanisms include, but are not restricted to production of immunosuppressive cytokines and prostaglandins and immune suppressive cells. Using different vaccination protocols, tumour models and multicolour flow cytometry, we are able to show that liver sinusoidal endothelial cells (LSECs) are the dominant cells take up carcino embryonic antigen (CEA), cross-presenting it to CD8+ T cells. These tumour specific T cells show a tolerance associated phenotype and are less effective eliminating the CEA-expressing MC–38 tumour cell-line. These results demonstrate a new pathway through tumours silence specific immune response. Further investigation of this mechanism in patients with colorectal carcinoma is important for the design of sufficient immunotherapeutic protocols.

CD8 - LSEC - immune suppression - tolerance - tumour