COPS5 and neoplasm: For example, berberine specifically binds to CSN5 and inhibits its activity, destabilizing PD-L1 and preventing the activation of Tregs in the TME (69); modified Bu-Zhong-Yi-Qi Decoction inhibits tumor PD-L1 expression via the PI3K/AKT pathway, while also reducing PD-1 expression on Tregs, thereby weakening their immunosuppressive effects (Xu R. et al., 2020); similarly curcumin lowers PD-1 and TIM-3 expression on Tregs, reducing their suppressive function, although the study has not explored the precise regulatory mechanisms involved (Liu et al., 2021).