CD274 and neoplasm: Extracellular lactate concentrations in the cerebral cortex vary during the day (Naylor et al., 2012), and Bmal1, a clock gene, regulates the expression of pyruvate kinase M2 (PKM2) and hence lactate production, which is required for the expression of the immune checkpoint protein PD-L1 (programmed cell death ligand 1) in tumor cells and immune cells (Palsson-McDermott et al., 2015; Deng et al., 2018; Figure 2).