Cancer immunotherapy involves blocking the interactions between the PD-1/PD-L1 immune checkpoints with antibodies. This has shown unprecedented positive outcomes in clinics. Particularly, the PD-L1 antibody therapy has shown the efficiency in blocking membrane PD-L1 and efficacy in treating some advanced carcinoma. However, this therapy has limited effects on many solid tumors, suspecting to be relevant to PD-L1 located in other cellular compartments, where they play additional roles and are associated with poor prognosis. In this review, we highlight the advances of 3 current strategies on PD-1/PD-L1 based immunotherapy, summarize cellular distribution of PD-L1, and review the versatile functions of intracellular PD-L1. The intracellular distribution and function of PD-L1 may indicate why not all antibody blockade is able to fully stop PD-L1 biological functions and effectively inhibit tumor growth. In this regard, gene silencing may have advantages over antibody blockade on suppression of PD-L1 sources and functions. Apart from cancer cells, PD-L1 silencing on host immune cells such as APC and DC can also enhance T cell immunity, leading to tumor clearance. Moreover, the molecular regulation of PD-L1 expression in cells is being elucidated, which helps identify potential therapeutic molecules to target PD-L1 production and improve clinical outcomes. Based on our understandings of PD-L1 distribution, regulation, and function, we prospect that the more effective PD-L1-based cancer immunotherapy will be combination therapies.

The manifestation of acute kidney injury (AKI) is associated with poor patient outcomes, with treatment options limited to hydration or renal replacement therapies. The onset of AKI is often associated with a surfeit of reactive oxygen species. Here, it is shown that selenium‐doped carbon quantum dots (SeCQDs) have broad‐spectrum antioxidant properties and prominent renal accumulation in both healthy and AKI mice. Due to these properties, SeCQDs treat or prevent two clinically relevant cases of AKI induced in murine models by either rhabdomyolysis or cisplatin using only 1 or 50 µg per mouse, respectively. The attenuation of AKI in both models is confirmed by blood serum measurements, kidney tissue staining, and relevant biomarkers. The therapeutic efficacy of SeCQDs exceeds amifostine, a drug approved by the Food and Drug Administration that also acts by scavenging free radicals. The findings indicate that SeCQDs show great potential as a treatment option for AKI and possibly other ROS‐related diseases.