Klrb1, also known as CD161, encodes an inhibitory receptor expressed on various immune cells and is involved in immune checkpoint regulation [7]. It has been implicated in multiple biological processes related to immunity and may influence immune cell-mediated killing of tumor cells, thus affecting tumor progression [4,5].

In glioma, CD161 was enriched in high-grade and IDH-wildtype gliomas, acting as a biomarker for the mesenchymal subtype and an independent prognostic factor. It inhibited T-cell cytotoxicity, and its expression dynamically evolved during gliomagenesis, promoting glioma progression [1]. In early-relapse hepatocellular carcinoma, CD8+ T cells in recurrent tumors overexpressed Klrb1 (CD161) and displayed a low-cytotoxic state, associated with a worse prognosis [2]. Genetic inactivation of Klrb1 enhanced T-cell-mediated killing of glioma cells in vitro and anti-tumor function in vivo [3]. In breast invasive carcinoma, decreased Klrb1 expression was associated with poor prognosis, increased tumor cell proliferation, migration, and invasion, and was related to the immune microenvironment [8]. In lung adenocarcinoma, Klrb1 expression was lower in cancer tissue, affected immune-related pathways and the MAPK/ERK signaling pathway, thus modulating cell growth and proliferation [6]. Klrb1 knockout in mice disrupted immune and metabolic functions in the liver, potentially leading to chronic inflammation and malignancy risks [7].

In summary, Klrb1 plays a crucial role in immune-related biological processes, especially in the context of various cancers and liver diseases. Gene knockout models, such as the Klrb1 KO mouse model, have been instrumental in revealing its functions in these disease conditions, highlighting its potential as a therapeutic target and biomarker.

References:

1. Di, Wang, Fan, Wenhua, Wu, Fan, Kahlert, Ulf Dietrich, Zhang, Wei. 2021. Clinical characterization and immunosuppressive regulation of CD161 (KLRB1) in glioma through 916 samples. In Cancer science, 113, 756-769. doi:10.1111/cas.15236. https://pubmed.ncbi.nlm.nih.gov/34881489/

2. Sun, Yunfan, Wu, Liang, Zhong, Yu, Yang, Xinrong, Fan, Jia. 2020. Single-cell landscape of the ecosystem in early-relapse hepatocellular carcinoma. In Cell, 184, 404-421.e16. doi:10.1016/j.cell.2020.11.041. https://pubmed.ncbi.nlm.nih.gov/33357445/

3. Mathewson, Nathan D, Ashenberg, Orr, Tirosh, Itay, Suvà, Mario L, Wucherpfennig, Kai W. 2021. Inhibitory CD161 receptor identified in glioma-infiltrating T cells by single-cell analysis. In Cell, 184, 1281-1298.e26. doi:10.1016/j.cell.2021.01.022. https://pubmed.ncbi.nlm.nih.gov/33592174/

4. Liang, Chunyun, Chen, Yue, Chen, Si, Shi, Qiuyan, Wang, Peijuan. 2023. KLRB1 is a novel prognostic biomarker in endometrial cancer and is associated with immune infiltration. In Translational cancer research, 12, 3641-3652. doi:10.21037/tcr-23-697. https://pubmed.ncbi.nlm.nih.gov/38192989/

5. Zhu, Yaoyao, Zhang, Huajie, Shao, Ruoyang, Lu, Peiyuan, Ma, Zhongrui. 2024. Comprehensive pan-cancer analysis of KLRB1-CLEC2D pair and identification of small molecule inhibitors to disrupt their interaction. In International immunopharmacology, 140, 112908. doi:10.1016/j.intimp.2024.112908. https://pubmed.ncbi.nlm.nih.gov/39133960/

6. Xu, Siwei, Xu, Yujian, Chai, Wenjun, Pan, Hongyu, Yan, Mingxia. 2024. KLRB1 expression is associated with lung adenocarcinoma prognosis and immune infiltration and regulates lung adenocarcinoma cell proliferation and metastasis through the MAPK/ERK pathway. In Journal of thoracic disease, 16, 3764-3781. doi:10.21037/jtd-24-8. https://pubmed.ncbi.nlm.nih.gov/38983163/

7. Yang, Shuqi, Luo, Tingting, Liu, Haoran, Li, Mingzhou, Lu, Lu. 2024. Klrb1 Loss Promotes Chronic Hepatic Inflammation and Metabolic Dysregulation. In Genes, 15, . doi:10.3390/genes15111444. https://pubmed.ncbi.nlm.nih.gov/39596644/

8. He, Jin-Rong, Li, Dan, Zhang, Qun-Xian, Chen, Shan-Shan, Chen, Jiu-Ling. 2023. Inhibiting KLRB1 expression is associated with impairing cancer immunity and leading to cancer progression and poor prognosis in breast invasive carcinoma patients. In Aging, 15, 13265-13286. doi:10.18632/aging.205239. https://pubmed.ncbi.nlm.nih.gov/37988189/