Cd276, also known as B7-H3, is an immunoregulatory protein belonging to the B7 family. It plays a crucial role in the tumor microenvironment (TME), participating in processes such as immune evasion, tumor cell proliferation, metastasis, and therapeutic resistance. It is involved in the epithelial-mesenchymal transition (EMT) pathway and is an important immune checkpoint molecule [1,3,4]. Genetic models, like gene knockout mouse models, are valuable for studying its functions.

In a chemically-induced murine model of head and neck squamous cell carcinoma, the role of Cd276 was studied. ITGB6 was identified as a key gene mediating differential responses to anti-Cd276 treatment. ITGB6 regulates the expression of CX3CL1, which recruits and activates PF4+ macrophages. Inhibition of the CX3CL1-CX3CR1 axis enhances sensitivity to anti-Cd276 treatment [5].

In esophageal squamous cell carcinoma, Cd276 knockout (CD276wKO) and conditional knockout (CD276cKO) mouse models were established. Depletion of Cd276 inhibited tumorigenesis and progression, reduced the formation of neutrophil extracellular trap networks (NETs) via the CXCL1-CXCR2 signaling axis, and augmented natural killer (NK) cells [6].

In bladder cancer, genetic ablation of Cd276 in tumor-associated macrophages (TAMs) 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 conclusion, Cd276 plays significant roles in immune evasion and tumor progression in various cancers. Studies using KO and CKO mouse models have revealed its functions in regulating immune cell infiltration, NET formation, and efferocytosis in specific cancer types, highlighting its potential as a therapeutic target in cancer immunotherapy.

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/