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Programmed cell death protein‐1 (PD‐1)/programmed death ligand‐1 (PD‐L1) immune checkpoint blockade as a breakthrough in cancer immunotherapy has shown unprecedented positive outcomes in the clinic. However, the overall effectiveness of PD‐L1 antibody is less than expected. An increasing number of studies have demonstrated that PD‐L1 is widely distributed and expressed not only on the cell membrane but also on the inside of the cells as well as on the extracellular vesicles secreted by tumour cells. Both endogenous and exogenous PD‐L1 play significant roles in influencing the therapeutic effect of anti‐tumour immunity. Herein, we mainly focused on the distribution and function of PD‐L1 and further summarized the potential targeted therapeutic strategies. More importantly, in addition to taking the overall expression abundance of PD‐L1 as a predictive indicator for selecting corresponding PD‐1/PD‐L1 monoclonal antibodies (mAbs), we also proposed that personalized combination therapies based on the different distribution of PD‐L1 are worth attention to achieve more efficient and effective therapeutic outcomes in cancer patients. LINKED ARTICLES: This article is part of a themed issue on Cancer Microenvironment and Pharmacological Interventions. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.2/issuetoc [ABSTRACT FROM AUTHOR]