Shi Nana, Luo Yingwan, Xu Ying, Liang Junyu, Ma An, Gan Yichao, Wu Bowen
Department of Hematology-oncology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China.
Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
J Oncol. 2021 Nov 25;2021:4824868. doi: 10.1155/2021/4824868. eCollection 2021.
B-cell acute lymphoblastic leukemia is the most common malignant tumor in children. About 10-15% of patients will relapse with a 5-year OS of 57.5% for the past 20 years. As tumor microenvironment plays an important role in the disease process, many types of immunotherapy are approached. New immunotherapies including CAR-T cells have been developed for refractory B-ALL treatment. However, CAR-T treatment faces several problems, including loss of the target antigen and in vivo T-cell persistence. Here, we analyzed the tumor microenvironment of pediatric B-ALL patients in TARGET database. Using Cox analysis and PPI network, we finally sorted out the DAP10 gene. We found that DAP10 was hardly expressed in leukemic B cells. DAP10 was downregulated in B-ALL compared with normal individuals, and low expression level of DAP10 predicted poor survival. Furthermore, we found the tumor microenvironment was different in DAP10 high and low expression children. The CD8+ T cells might be hard to activate and more likely to suffer from exhaustion in DAP10 lowly expressed children. In conclusion, our results showed that DAP10 was a well biomarker to indicate the prognosis and tumor microenvironment in pediatric B-ALL. The treatment strategy of immunotherapy for the leukemic children with DAP10 lowly expressed should be adjusted if needed.
B细胞急性淋巴细胞白血病是儿童最常见的恶性肿瘤。约10%-15%的患者会复发，在过去20年中5年总生存率为57.5%。由于肿瘤微环境在疾病过程中起重要作用，人们探索了多种免疫疗法。包括嵌合抗原受体T细胞（CAR-T）在内的新型免疫疗法已被开发用于难治性B细胞急性淋巴细胞白血病（B-ALL）的治疗。然而，CAR-T治疗面临几个问题，包括靶抗原丢失和体内T细胞持久性。在此，我们分析了TARGET数据库中儿童B-ALL患者的肿瘤微环境。通过Cox分析和蛋白质-蛋白质相互作用（PPI）网络，我们最终筛选出了DAP10基因。我们发现DAP10在白血病B细胞中几乎不表达。与正常个体相比，B-ALL中DAP10表达下调，且DAP10低表达预示着较差的生存率。此外，我们发现DAP10高表达和低表达儿童的肿瘤微环境不同。在DAP10低表达的儿童中，CD8+T细胞可能难以激活且更容易耗竭。总之，我们的结果表明DAP10是指示儿童B-ALL预后和肿瘤微环境的良好生物标志物。对于DAP10低表达的白血病儿童，如有必要应调整免疫治疗策略。
