For example, a comprehensive pan-cancer analysis demonstrated a strong association between the upregulation of immunosuppressive molecules like PD-L1 and CTLA-4, and the downregulation of PER1, PER2, and PER3 genes, underscoring the impact of disrupted clock genes on T cell exhaustion and immune evasion in the TME (Wu et al., 2019). This evidence concerns the gene PER2 and cancer.