Cd276, also known as B7-H3, is an immunoregulatory protein belonging to the B7 family. It plays a crucial role in the immune system, especially in the context of cancer, by participating in tumor microenvironment (TME) shaping and development. It is an important immune checkpoint molecule in the epithelial mesenchymal transition (EMT) pathway [1,3,4].

In bladder cancer, genetic ablation of CD276 in tumor-associated macrophages (TAMs) using a mouse model blocks efferocytosis and enhances the expression of major histocompatibility complex class II (MHCII) of TAMs, increasing CD4 + and cytotoxic CD8 + T cell infiltration of the tumor. This shows that CD276 expressed on TAMs plays a role in diminishing the immune response against tumors [2]. In esophageal squamous cell carcinoma (ESCC), conditional knockout of CD276 in epithelial cells of a mouse model leads to down-regulation of CXCL1, reduction of neutrophil extracellular trap networks (NETs) via the CXCL1-CXCR2 signaling axis, and an increase in natural killer (NK) cells. Depletion of CD276 inhibits tumorigenesis and progression of ESCC, suggesting that CD276 is involved in immune escape mechanisms in ESCC [5].

In conclusion, Cd276 is a key immune-related gene. Through gene-knockout mouse models in bladder cancer and ESCC, it has been revealed that Cd276 is involved in immune evasion processes in these cancers. These findings highlight the importance of Cd276 in tumor-immune interactions and suggest its potential as a therapeutic target in cancer treatment [2,5].

References:

1. Zhou, Wu-Tong, Jin, Wei-Lin. 2021. B7-H3/CD276: An Emerging Cancer Immunotherapy. In Frontiers in immunology, 12, 701006. doi:10.3389/fimmu.2021.701006. https://pubmed.ncbi.nlm.nih.gov/34349762/

2. Cheng, Maosheng, Chen, Shuang, Li, Kang, Li, Yang, Peng, Liang. 2024. CD276-dependent efferocytosis by tumor-associated macrophages promotes immune evasion in bladder cancer. In Nature communications, 15, 2818. doi:10.1038/s41467-024-46735-5. https://pubmed.ncbi.nlm.nih.gov/38561369/

3. Getu, Ayechew Adera, Tigabu, Abiye, Zhou, Ming, Fodstad, Øystein, Tan, Ming. 2023. New frontiers in immune checkpoint B7-H3 (CD276) research and drug development. In Molecular cancer, 22, 43. doi:10.1186/s12943-023-01751-9. https://pubmed.ncbi.nlm.nih.gov/36859240/

4. Liu, Shengzhuo, Liang, Jiayu, Liu, Zhihong, Lu, Yiping, Wang, Xianding. 2021. The Role of CD276 in Cancers. In Frontiers in oncology, 11, 654684. doi:10.3389/fonc.2021.654684. https://pubmed.ncbi.nlm.nih.gov/33842369/

5. Xiong, Gan, Chen, Zhi, Liu, Qianwen, Chen, Demeng, Zhou, Qimin. 2024. CD276 regulates the immune escape of esophageal squamous cell carcinoma through CXCL1-CXCR2 induced NETs. In Journal for immunotherapy of cancer, 12, . doi:10.1136/jitc-2023-008662. https://pubmed.ncbi.nlm.nih.gov/38724465/