SLAMF6, also known as Signaling lymphocyte activation molecule family member 6, is a T cell co-receptor. It plays a crucial role in T cell activation and is involved in immune-related signaling pathways. Its functions are vital for the normal operation of the immune system, and genetic models like KO mouse models are valuable for studying its roles [1,2,3,4,5].

In KO mouse models, Slamf6-/-B6 CD4+ T cells transferred into co-isogenic bm12 mice led to SLE-like autoimmunity, indicating that Slamf6 negatively regulates autoimmunity [4]. In the Eμ-TCL1 chronic lymphocytic leukemia and B16 melanoma mouse models, targeting Slamf6 corrected CD8+ T-cell dysfunction and affected tumor growth, suggesting it as a potential therapeutic target in cancer [3]. Also, activated Pmel-1xSLAMF6-/-CD8+ T cells showed improved polyfunctionality and strong tumor cytolysis, revealing Slamf6 as an inhibitory immune receptor in tumor-related immune responses [5].

In conclusion, Slamf6 is a key regulator in the immune system, with its absence in KO mouse models revealing its roles in autoimmunity and cancer. These model-based studies highlight its importance in specific disease areas, suggesting potential therapeutic implications in treating autoimmune diseases and cancer by targeting Slamf6.

References:

1. Gartshteyn, Yevgeniya, Askanase, Anca D, Song, Ruijiang, Adam, Kieran, Mor, Adam. 2022. SLAMF6 compartmentalization enhances T cell functions. In Life science alliance, 6, . doi:10.26508/lsa.202201533. https://pubmed.ncbi.nlm.nih.gov/36622343/

2. Dragovich, Matthew A, Adam, Kieran, Strazza, Marianne, Peled, Michael, Mor, Adam. 2019. SLAMF6 clustering is required to augment T cell activation. In PloS one, 14, e0218109. doi:10.1371/journal.pone.0218109. https://pubmed.ncbi.nlm.nih.gov/31199820/

3. Yigit, Burcu, Wang, Ninghai, Ten Hacken, Elisa, Engel, Pablo, Terhorst, Cox. 2019. SLAMF6 as a Regulator of Exhausted CD8+ T Cells in Cancer. In Cancer immunology research, 7, 1485-1496. doi:10.1158/2326-6066.CIR-18-0664. https://pubmed.ncbi.nlm.nih.gov/31315913/

4. Wang, Ninghai, Keszei, Marton, Halibozek, Peter, Engel, Pablo, Terhorst, Cox. 2016. Slamf6 negatively regulates autoimmunity. In Clinical immunology (Orlando, Fla.), 173, 19-26. doi:10.1016/j.clim.2016.06.009. https://pubmed.ncbi.nlm.nih.gov/27368806/

5. Hajaj, Emma, Eisenberg, Galit, Klein, Shiri, Veillette, Andre, Lotem, Michal. 2020. SLAMF6​ deficiency augments tumor killing and skews toward an effector phenotype revealing it as a novel T cell checkpoint. In eLife, 9, . doi:10.7554/eLife.52539. https://pubmed.ncbi.nlm.nih.gov/32122464/