Cd276, also known as B7-H3, is an immunoregulatory protein belonging to the B7 family. It plays a key role in cancer progression, participating in tumor microenvironment (TME) shaping. It is involved in the epithelial mesenchymal transition (EMT) pathway and is selectively expressed in tumor cells and immune cells within the TME [1,3,4].

Genetic ablation of Cd276 in tumor-associated macrophages (TAMs) in a mouse model of bladder cancer blocked efferocytosis, enhanced the expression of major histocompatibility complex class II (MHCII) of TAMs, and increased CD4+ and cytotoxic CD8+ T cell infiltration of the tumor [2]. In a chemically-induced murine model of head and neck squamous cell carcinoma, the role of ITGB6 in mediating differential responses to anti-Cd276 treatment was identified, with ITGB6 regulating a chemokine axis that affects macrophage infiltration and anti-Cd276 treatment sensitivity [5]. In an esophageal squamous cell carcinoma mouse model, conditional knockout of Cd276 in epithelial cells downregulated CXCL1, reduced neutrophil extracellular trap network (NETs) formation via the CXCL1-CXCR2 axis, and augmented natural killer (NK) cells [6].

In conclusion, Cd276 is crucial in cancer-related immune evasion. KO/CKO mouse models have revealed its role in modulating immune cell infiltration, efferocytosis, and immune escape mechanisms in bladder, head and neck, and esophageal squamous cell carcinomas, highlighting its potential as a therapeutic target in these cancer types.

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. Zhang, Caihua, Li, Kang, Zhu, Hongzhang, Wang, Cheng, Chen, Demeng. 2024. ITGB6 modulates resistance to anti-CD276 therapy in head and neck cancer by promoting PF4+ macrophage infiltration. In Nature communications, 15, 7077. doi:10.1038/s41467-024-51096-0. https://pubmed.ncbi.nlm.nih.gov/39152118/

6. 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/