De Sanctis Juan Bautista, Garmendia Jenny Valentina, Duchová Hana, Valentini Viktor, Puskasu Alex, Kubíčková Agáta, Hajdúch Marián
Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, 77900 Olomouc, Czech Republic.
Czech Advanced Technologies and Research Institute (CATRIN), 77900 Olomouc, Czech Republic.
Cancers (Basel). 2024 Jul 24;16(15):2630. doi: 10.3390/cancers16152630.
Lck, a member of the Src kinase family, is a non-receptor tyrosine kinase involved in immune cell activation, antigen recognition, tumor growth, and cytotoxic response. The enzyme has usually been linked to T lymphocyte activation upon antigen recognition. Lck activation is central to CD4, CD8, and NK activation. However, recently, it has become clearer that activating the enzyme in CD8 cells can be independent of antigen presentation and enhance the cytotoxic response. The role of Lck in NK cytotoxic function has been controversial in a similar fashion as the role of the enzyme in CAR T cells. Inhibiting tyrosine kinases has been a highly successful approach to treating hematologic malignancies. The inhibitors may be useful in treating other tumor types, and they may be useful to prevent cell exhaustion. New, more selective inhibitors have been documented, and they have shown interesting activities not only in tumor growth but in the treatment of autoimmune diseases, asthma, and graft vs. host disease. Drug repurposing and bioinformatics can aid in solving several unsolved issues about the role of Lck in cancer. In summary, the role of Lck in immune response and tumor growth is not a simple event and requires more research.
Lck是Src激酶家族的成员,是一种非受体酪氨酸激酶,参与免疫细胞激活、抗原识别、肿瘤生长和细胞毒性反应。该酶通常与抗原识别后T淋巴细胞的激活有关。Lck激活对于CD4、CD8和NK激活至关重要。然而,最近越来越清楚的是,在CD8细胞中激活该酶可以独立于抗原呈递,并增强细胞毒性反应。Lck在NK细胞毒性功能中的作用一直存在争议,类似于该酶在CAR-T细胞中的作用。抑制酪氨酸激酶一直是治疗血液系统恶性肿瘤的一种非常成功的方法。这些抑制剂可能对治疗其他肿瘤类型有用,并且可能有助于防止细胞耗竭。已经有新的、更具选择性的抑制剂被记录下来,它们不仅在肿瘤生长方面表现出有趣的活性,而且在治疗自身免疫性疾病、哮喘和移植物抗宿主病方面也有活性。药物重新利用和生物信息学有助于解决关于Lck在癌症中的作用的几个未解决问题。总之,Lck在免疫反应和肿瘤生长中的作用不是一个简单的问题,需要更多的研究。