Cd274-KO Mouse

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, enabling cancer cells to escape the immune system's surveillance, leading to tumor immunosuppression [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, suggesting it as a potential biomarker for multiple types of cancers [1]. In colorectal cancer, Cd274 on immune cells was associated with good prognosis, while on tumor cells, the outcomes were heterogeneous and it did not meet the requirements of a prognostic marker [2]. Genomic profiling of a malignant peripheral nerve sheath tumor case revealed Cd274/PD-L1 amplification, which could potentially guide immune checkpoint inhibitor therapy [4]. Also, studies identified ubiquitin-specific protease 22 (USP22) as a deubiquitinase of Cd274, and its genetic depletion inhibited liver cancer growth in an immune-dependent manner and improved the efficacy of Cd274-targeted immunotherapy in mice [5]. Baicalein, a monomer of traditional Chinese medicine, was found to tether Cd274/PD-L1 for autophagic degradation, inhibiting tumor development by boosting T-cell-mediated antitumor immunity [6].

In conclusion, Cd274 is a crucial immune checkpoint protein involved in tumor immunosuppression. Model-based research, especially in mouse models, has shown its significance in various cancers. These findings contribute to understanding the role of Cd274 in disease development and highlight its potential as a biomarker and therapeutic target in cancer immunotherapy.

References:

1. Park, Ji Hyun, Luchini, Claudio, Nottegar, Alessia, Lim, Beom Jin, Smith, Lee. 2023. Effect of CD274 (PD-L1) overexpression on survival outcomes in 10 specific cancers: a systematic review and meta-analysis. In Journal of clinical pathology, 76, 450-456. doi:10.1136/jcp-2023-208848. https://pubmed.ncbi.nlm.nih.gov/37130750/

2. Alexander, Peter G, McMillan, Donald C, Park, James H. 2020. A meta-analysis of CD274 (PD-L1) assessment and prognosis in colorectal cancer and its role in predicting response to anti-PD-1 therapy. In Critical reviews in oncology/hematology, 157, 103147. doi:10.1016/j.critrevonc.2020.103147. https://pubmed.ncbi.nlm.nih.gov/33278675/

3. Gou, Qian, Dong, Chen, Xu, Huihui, Shi, Juanjuan, Hou, Yongzhong. 2020. PD-L1 degradation pathway and immunotherapy for cancer. In Cell death & disease, 11, 955. doi:10.1038/s41419-020-03140-2. https://pubmed.ncbi.nlm.nih.gov/33159034/

4. Na, Kiyong, Kim, Hong Jun. . CD274/PD-L1 copy number gained malignant peripheral nerve sheath tumor: A case report and literature review. In Medicine, 104, e41165. doi:10.1097/MD.0000000000041165. https://pubmed.ncbi.nlm.nih.gov/40184088/

5. Huang, Xing, Zhang, Qi, Lou, Yu, Liang, Tingbo, Bai, Xueli. 2019. USP22 Deubiquitinates CD274 to Suppress Anticancer Immunity. In Cancer immunology research, 7, 1580-1590. doi:10.1158/2326-6066.CIR-18-0910. https://pubmed.ncbi.nlm.nih.gov/31399419/

6. Hao, Bingjie, Lin, Shumeng, Liu, Haipeng, Xia, Qing, Fan, Lihong. 2024. Baicalein tethers CD274/PD-L1 for autophagic degradation to boost antitumor immunity. In Autophagy, 21, 917-933. doi:10.1080/15548627.2024.2439657. https://pubmed.ncbi.nlm.nih.gov/39710370/