Modulation of dendritic cells phenotype and functions by irradiated and non-irradiated lung cancer fibroblasts. An in vitro study.

Abstract

Stromal cells in the tumor microenvironment (TME) interacts with cancer cells and affect their behavior in diverse manners. In this study, we investigated in vitro the mechanisms by which non-irradiated and irradiated cancer-associated fibroblasts (CAFs) isolated from patients with non-small cell lung carcinoma (NSCLC) affected the phenotype and function of monocyte-derived dendritic cells (Mo-DCs) isolated from blood samples gathered for healthy blood donors. The expression of CD14, CD1a and CD209 was lower in Mo-DCs in co-culture with CAFs than in control cells. Further, the expression of co-stimulatory molecules CD80 and CD86 was down-regulated in culture with CAF supernatant. For functional markers CD40 and HLA-DR, we could observe that expression was suppressed in CAF-CM and co-culture experiments. Our results demonstrated that CAF-secreted molecules could suppress antigen uptake capacity and migratory ability for Mo-DCs. For Mo-DCs priming of CD4+ T-cell, we could see that both CAF-CM and co-culture conditions blocked the priming of T-cells. Irradiation of CAFs with fractioned medium-high dose induced in some settings enhanced expression of surface markers as well as increased functionality of Mo-DCs. This study demonstrates that there is a cross-talk between CAFs and Mo-DCs were results indicates that CAFs educate Mo-DCs to become tolerogenic.