Here, we have investigated how BM-MSCs can be recruited and transformed into cancer associated fibroblasts (CAF)-like by HNSCC cells and how cross-talk between tumor and stromal cells supports the onset of a pro-metastatic state by increasing tumor cell migration, invasiveness and stemness as well as EMT program by involving PD-L1 through AKT and MAPK signaling pathways. This evidence concerns the gene CD274 and cancer.