DAP10 Predicted the Outcome of Pediatric B-Cell Acute Lymphoblastic Leukemia and Was Associated with the T-Cell Exhaustion

Nana Shi; Yingwan Luo; Ying Xu; Junyu Liang; An Ma; Yichao Gan; Bowen Wu

doi:10.1155/2021/4824868

DAP10 Predicted the Outcome of Pediatric B-Cell Acute Lymphoblastic Leukemia and Was Associated with the T-Cell Exhaustion

J Oncol. 2021 Nov 25:2021:4824868. doi: 10.1155/2021/4824868. eCollection 2021.

Authors

Nana Shi¹, Yingwan Luo², Ying Xu², Junyu Liang³, An Ma⁴, Yichao Gan⁵, Bowen Wu^{2

6}

Affiliations

¹ Department of Hematology-oncology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China.
² Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
³ Department of Rheumatology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
⁴ School of Basic Medical Sciences and Forensic Medicine, Hangzhou Medical College, Hangzhou, China.
⁵ Institute of Genetics, Zhejiang University and Department of Genetics, Zhejiang University School of Medicine, Hangzhou, China.
⁶ Cancer Center, Zhejiang University, Hangzhou, China.

Abstract

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.