CD274 and cancer: Furthermore, in tumor tissue of patients with non-small cell lung cancer (NSCLC) receiving opioid analgesia, M3G specifically bound to TLR4 and upregulated PD-L1 expression via the PI3K signaling pathway, the overexpression of PD-L1 negatively regulated the number and activation of cytotoxic T lymphocytes (CTL), which indicated that the upregulation of PD-L1/PD-1 affects the amount and function of human CTL, participating in the opioid analgesia mechanism of cancer pain patients [55].