Cd274, also known as Programmed cell death ligand 1 (PD-L1), is an essential immune checkpoint protein. It binds to programmed death 1 (PD-1) on T-lymphocytes. The binding inhibits T cell proliferation and activity, leading to tumor immunosuppression, allowing cancer cells to escape immune surveillance [3].

A large meta-analysis including 57,322 patients from 250 eligible studies found that CD274 (PD-L1) overexpression was associated with worse overall survival in non-small cell lung cancer, hepatocellular carcinoma, pancreatic cancer, renal cell carcinoma and colorectal cancer [1]. In colorectal cancer, CD274 on immune cells was associated with good prognosis, while its expression on tumour cells had heterogeneous outcomes and did not meet the requirements of a prognostic marker [2]. Identifying ubiquitin-specific protease 22 (USP22) as a novel deubiquitinase of CD274, genetic depletion of USP22 inhibited liver cancer growth in an immune-system-dependent manner, increased tumor immunogenicity and tumor-infiltrating lymphocytes, and improved therapeutic efficacy of CD274-targeted immunotherapy in mice [4].

In conclusion, Cd274 is a crucial immune checkpoint protein involved in tumor immunosuppression. Its overexpression is related to poor prognosis in multiple cancers. Mouse models, such as those with genetic depletion of related regulators like USP22, help reveal its role in cancer development and response to immunotherapy, providing insights for potential cancer treatment strategies.