CD37,也称为TSPAN26,是一种重要的跨膜4超家族(TM4SF)成员,主要表达在成熟的B细胞和部分T细胞上。CD37是一种具有四个跨膜结构域和一个主要细胞外环的糖蛋白,其基因位于人类19号染色体上。CD37在免疫调节和肿瘤抑制中发挥关键作用,是多种B细胞淋巴瘤免疫治疗的重要靶点[8,9]。
CD37在多种疾病中发挥重要作用。例如,在非酒精性脂肪性肝病(NAFLD)中,CD37的表达与疾病的严重程度和预后相关[5]。在血小板功能方面,CD37参与调节血小板的活化反应,与血栓形成有关[6]。此外,CD37的表达与B细胞淋巴瘤的预后相关,CD37阳性患者的生存率显著高于CD37阴性患者[7]。
在B细胞淋巴瘤中,CD37的表达受到多种因素的调控。例如,CD20的表达可以稳定CD37在细胞膜上的表达,从而影响抗CD37免疫疗法的疗效[1]。此外,转录因子IRF8可以激活CD37的表达,而PI3Kδ的激活和IL-6的过表达可以导致CD37的丢失,从而对CD37靶向的抗体药物偶联物(ADC)产生耐药性[2,3]。
在非小细胞肺癌(NSCLC)中,CD37的表达与脑转移的发生相关。CD37的表达下调与非小细胞肺癌患者发生脑转移的风险增加相关[4]。
综上所述,CD37在多种生物学过程中发挥重要作用,包括免疫调节、肿瘤抑制、血小板功能调节和疾病发生。CD37的表达受到多种因素的调控,其表达水平与多种疾病的预后相关。深入研究CD37的生物学功能和调控机制,有助于开发新的免疫治疗策略,提高疾病的治疗效果。
参考文献:
1. Bobrowicz, Malgorzata, Kusowska, Aleksandra, Krawczyk, Marta, Prochorec-Sobieszek, Monika, Winiarska, Magdalena. 2024. CD20 expression regulates CD37 levels in B-cell lymphoma - implications for immunotherapies. In Oncoimmunology, 13, 2362454. doi:10.1080/2162402X.2024.2362454. https://pubmed.ncbi.nlm.nih.gov/38846084/
2. Elfrink, Suraya, Ter Beest, Martin, Janssen, Luuk, Scheijen, Blanca, van Spriel, Annemiek B. . IRF8 is a transcriptional activator of CD37 expression in diffuse large B-cell lymphoma. In Blood advances, 6, 2254-2266. doi:10.1182/bloodadvances.2021004366. https://pubmed.ncbi.nlm.nih.gov/35086136/
3. Arribas, Alberto J, Napoli, Sara, Gaudio, Eugenio, Davids, Matthew S, Bertoni, Francesco. . PI3Kδ activation, IL-6 overexpression, and CD37 loss cause resistance to naratuximab emtansine in lymphomas. In Blood advances, 8, 6268-6281. doi:10.1182/bloodadvances.2023012291. https://pubmed.ncbi.nlm.nih.gov/39374583/
4. Dohm, Ammoren, Su, Jing, McTyre, Emory R, Chan, Michael D, Ruiz, Jimmy. 2019. Identification of CD37, cystatin A, and IL-23A gene expression in association with brain metastasis: analysis of a prospective trial. In The International journal of biological markers, 34, 90-97. doi:10.1177/1724600818803104. https://pubmed.ncbi.nlm.nih.gov/30854931/
5. Zhang, Jiayi, Wang, Lingfang, Jiang, Meixiu. . Diagnostic value of sphingolipid metabolism-related genes CD37 and CXCL9 in nonalcoholic fatty liver disease. In Medicine, 103, e37185. doi:10.1097/MD.0000000000037185. https://pubmed.ncbi.nlm.nih.gov/38394483/
6. Sowa, Marcin A, Hannemann, Carmen, Pinos Cabezas, Ivan, Berger, Jeffrey S, Barrett, Tessa J. 2025. Tetraspanin CD37 regulates platelet hyperreactivity and thrombosis. In Cardiovascular research, , . doi:10.1093/cvr/cvaf051. https://pubmed.ncbi.nlm.nih.gov/40126944/
7. Xu-Monette, Zijun Y, Li, Ling, Byrd, John C, van Spriel, Annemiek B, Young, Ken H. 2016. Assessment of CD37 B-cell antigen and cell of origin significantly improves risk prediction in diffuse large B-cell lymphoma. In Blood, 128, 3083-3100. doi:10.1182/blood-2016-05-715094. https://pubmed.ncbi.nlm.nih.gov/27760757/
8. Virtaneva, K I, Angelisová, P, Baumruker, T, Nevanlinna, H, Schröder, J. . The genes for CD37, CD53, and R2, all members of a novel gene family, are located on different chromosomes. In Immunogenetics, 37, 461-5. doi:. https://pubmed.ncbi.nlm.nih.gov/8436422/
9. Tomlinson, M G, Wright, M D. . Characterisation of mouse CD37: cDNA and genomic cloning. In Molecular immunology, 33, 867-72. doi:. https://pubmed.ncbi.nlm.nih.gov/8845018/