Ms4a4a, a member of the membrane-spanning 4-domains subfamily A, is selectively expressed in macrophage-lineage cells, monocytes, immature dendritic cells, M2 macrophages, plasma cells and mast cells [2,6,7]. It has diverse functions such as enhancing dectin-1-dependent NK cell-mediated resistance to metastasis, promoting FcεRI signal transduction in human mast cells, and regulating arginase 1 expression in macrophages under IL4 stimulation [2,5,7]. It is also involved in pathways like PI3K/AKT and JAK/STAT6 [1]. The gene is of great biological importance in immunity, tumor development, and potentially in neurodegenerative diseases [1,2,4]. Genetic models, especially KO mouse models, can be valuable in further exploring its functions.

In murine subcutaneous and orthotopic transplanted tumor models, in vivo inhibition of Ms4a4a curbs tumor growth, reshapes the tumor immune microenvironment, reduces infiltration of M2-TAMs and exhausted T cells, and increases infiltration of effector CD8+ T cells [1]. In glioblastoma in vivo models, inhibiting Ms4a4a and combining immune checkpoint blockade therapy effectively inhibits tumor growth, reduces M2 TAM infiltration, and enhances CD8+ T-cell infiltration [3]. In experimental models of tumor progression and metastasis, Ms4a4a-deficient macrophages have no impact on primary tumor growth but are essential for dectin-1-mediated activation of macrophages and NK cell-mediated metastasis control [2].

In conclusion, Ms4a4a plays crucial roles in immune-related biological processes and tumor development. The use of KO mouse models has revealed its significant impact on the tumor immune microenvironment and metastasis control, offering potential new approaches for cancer immunotherapy and highlighting its importance in understanding tumor-immune interactions [1,2,3].