CD274 and melanoma: In HCC, translational and clinical data suggest that reversal of T cell exhaustion through blockade of the PD-1/PD-L1 pathway, although effective, requires combined modulation of multiple co-inhibitory pathways that affect myeloid and other stromal components of the tumour microenvironment,41 suggesting therefore that T cell clonality may not be univocally associated with immune-responsiveness unlike melanoma and other more immune-sensitive malignancies.42