Cd47-KO Mouse

Cd47, or Cluster of Differentiation 47, is a protein expressed on both healthy and cancer cells. It plays a pivotal role in regulating the cytotoxic activity of myeloid cells by delivering a “don't eat me signal” when it binds to the Signal-regulatory protein alpha (SIRPα) receptor on myeloid cells. This interaction is part of a balance of signals transmitted through inhibitory and activating receptors, which is crucial for physiological tissue homeostasis [1].

In cancer research, anti-Cd47 antibody-based therapies have been investigated. In syngeneic immunocompetent mouse tumor models, the therapeutic effects of Cd47 blockade were found to depend on dendritic cell-mediated cross-priming of T cell responses rather than macrophage phagocytosis as previously thought, and were abrogated in T cell-deficient mice. Also, the antitumor effects required the cytosolic DNA sensor STING in CD11c + cells [3]. In glioblastoma, enhanced fatty acid metabolism promotes aggressive growth with Cd47-mediated immune evasion, and targeting the FAO-Cd47 axis may improve radioimmunotherapy [2].

In conclusion, Cd47 is essential in regulating the immune response, especially the interaction between myeloid cells and other cells. Studies using mouse models have revealed its significance in cancer, such as in promoting tumor immune evasion and influencing the efficacy of immunotherapies. Understanding Cd47 could potentially lead to the development of more effective cancer treatments.

References:

1. Logtenberg, Meike E W, Scheeren, Ferenc A, Schumacher, Ton N. . The CD47-SIRPα Immune Checkpoint. In Immunity, 52, 742-752. doi:10.1016/j.immuni.2020.04.011. https://pubmed.ncbi.nlm.nih.gov/32433947/

2. Jiang, Nian, Xie, Bowen, Xiao, Wenwu, Chen, Hong-Wu, Li, Jian Jian. 2022. Fatty acid oxidation fuels glioblastoma radioresistance with CD47-mediated immune evasion. In Nature communications, 13, 1511. doi:10.1038/s41467-022-29137-3. https://pubmed.ncbi.nlm.nih.gov/35314680/

3. Liu, Xiaojuan, Pu, Yang, Cron, Kyle, Fu, Yang-Xin, Xu, Meng Michelle. 2015. CD47 blockade triggers T cell-mediated destruction of immunogenic tumors. In Nature medicine, 21, 1209-15. doi:10.1038/nm.3931. https://pubmed.ncbi.nlm.nih.gov/26322579/