Klrc1, which encodes the NK cell inhibitory receptor NKG2A, is a key gene in the immune system. NKG2A, a potent NK cell immune checkpoint, specifically binds to HLA-E, a non-classical HLA class I molecule. This interaction transmits inhibitory signals that strongly impair NK cell function, thus being involved in the immunosuppressive tumor microenvironment (TME) and influencing immune-related biological processes [1].

In cancer research, KLRC1 knockout has shown promising results. In vitro, KLRC1 knockout (KO) NK cells exhibit significantly higher cytotoxicity against HLA-E+ solid tumor cell lines compared to wild-type (WT) NK cells [1]. In vivo, the adoptive transfer of human KLRC1 KO NK cells significantly delays tumor progression and increases survival in a xenogeneic mouse model of HLA-E+ metastatic breast cancer [1]. Also, in acute myeloid leukemia (AML), CD33-specific CAR-NK cells combined with Nuclease technology-based KLRC1 gene disruption demonstrate potent antileukemic killing activity in vitro and in vivo [2]. In addition, in keloids, the NKG2A/CD94 complex encoded by Klrc1 is specifically upregulated, which might contribute to the reduction of cytotoxic CD8+ T cells within the scar tissue boundary [3].

In conclusion, Klrc1 plays a crucial role in immune regulation, especially in the context of tumor-immune interactions. Studies using Klrc1 KO models have revealed its importance in tumor immunity, suggesting that targeting Klrc1 could be a potential strategy for improving NK cell-based cancer immunotherapies.