In the tumor microenvironment of CLL both the conversion of functional to exhausted T cells overexpressing the exhaustion marker PD-1 (Riches et al., 2013), and PD-L1 overexpression on the surface of leukemic cells, concur to exacerbate the physiological PD-1/PD-L1 inhibitory axis and hamper TCR-mediated T cell activation (Riches et al., 2013). The gene discussed is CD274; the disease is neoplasm.