Klrk1, encoding NKG2D, is a homodimeric lectin-like receptor. NKG2D can bind to its ligands expressed by cancer cells, playing a role in cancer immunosurveillance, and is involved in immune-related pathways [1,2]. It is highly expressed in immune cells and is of great biological importance in the body's immune response against tumors.

In lung adenocarcinoma, patients with high Klrk1 expression had improved overall and relapse-free survival, and in vitro studies indicated that Klrk1 inhibited tumor cell proliferation and migration [1]. In head and neck squamous cell carcinoma (HNSCC), Klrk1 was highly expressed and correlated with better prognosis and immune cell infiltration, especially of CD4/8(+) T lymphocytes [2]. In the context of antithyroid drug-induced agranulocytosis, the KLRC4-Klrk1 gene polymorphism was associated with susceptibility and progression, with patients carrying the rs2734565-C allele having a higher susceptibility and faster onset time [3]. Regulatory T cells suppress the formation of KLRK1-expressing effector CD8 T cells by limiting IL-2, which are distinct from conventional effector CD8+ T cells and show superior cell-killing abilities in vivo [4].

In conclusion, Klrk1 is crucial in immune-related biological functions, especially in tumor immunosurveillance. Studies in various disease models, such as in lung adenocarcinoma, HNSCC, and antithyroid drug-induced agranulocytosis, have shown its significance in disease prognosis and progression. Its role in the regulation of effector CD8 T cells by regulatory T cells also provides insights into immune-mediated disease mechanisms.

References:

1. Zhang, Yanan, Chen, Zeyang, Jiang, Aifang, Gao, Guanqi. 2022. KLRK1 as a prognostic biomarker for lung adenocarcinoma cancer. In Scientific reports, 12, 1976. doi:10.1038/s41598-022-05997-z. https://pubmed.ncbi.nlm.nih.gov/35132098/

2. Tan, Haosheng, Yang, Huaiyu, Qian, Jiaxin, Wei, Liyuan, Liu, Wensheng. . Involvement of KLRK1 in immune infiltration of head and neck squamous cell carcinoma correlates with favorable prognosis. In Medicine, 102, e34761. doi:10.1097/MD.0000000000034761. https://pubmed.ncbi.nlm.nih.gov/37565867/

3. He, Yayi, Ma, Pan, Luo, Yuanlin, Shi, Bingyin, Zhang, Bao. 2024. Novel Association of KLRC4-KLRK1 Gene Polymorphisms with Susceptibility and Progression of Antithyroid Drug-Induced Agranulocytosis. In Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association, 132, 17-22. doi:10.1055/a-2206-2242. https://pubmed.ncbi.nlm.nih.gov/38237612/

4. Tsyklauri, Oksana, Chadimova, Tereza, Niederlova, Veronika, Kovar, Marek, Stepanek, Ondrej. 2023. Regulatory T cells suppress the formation of potent KLRK1 and IL-7R expressing effector CD8 T cells by limiting IL-2. In eLife, 12, . doi:10.7554/eLife.79342. https://pubmed.ncbi.nlm.nih.gov/36705564/