Single‐Cell RNA‐Seq of T Cells in B‐ALL Patients Reveals an Exhausted Subset with Remarkable Heterogeneity

• Published in: Advanced science Vol. 8; no. 19; pp. e2101447 - n/a
• Main Authors: Wang, Xiaofang, Chen, Yanjuan, Li, Zongcheng, Huang, Bingyan, Xu, Ling, Lai, Jing, Lu, Yuhong, Zha, Xianfeng, Liu, Bing, Lan, Yu, Li, Yangqiu
• Format: Journal Article
• Language: English
• Published: Germany John Wiley & Sons, Inc 01.10.2021; John Wiley and Sons Inc; Wiley
• Subjects: B cell‐acute lymphoblastic leukemia; Blood; Bone marrow; Chemotherapy; Cytotoxicity; Genomics; heterogeneity; Humans; Immune system; Leukemia; Lymphocyte Count - methods; Lymphocytes; Lymphocytes, Tumor-Infiltrating - immunology; Patients; Precursor Cell Lymphoblastic Leukemia-Lymphoma - blood; Precursor Cell Lymphoblastic Leukemia-Lymphoma - immunology; RNA-Seq - methods; single‐cell RNA sequencing; T cell receptors; T cells; T-Lymphocyte Subsets - immunology; Tumors; single-cell RNA sequencing; B cell-acute lymphoblastic leukemia; T cells; heterogeneity
• ISSN: 2198-3844; 2198-3844
• DOI: 10.1002/advs.202101447

Characterization of functional T cell clusters is key to developing strategies for immunotherapy and predicting clinical responses in leukemia. Here, single‐cell RNA sequencing is performed with T cells sorted from the peripheral blood of healthy individuals and patients with B cell‐acute lymphoblastic leukemia (B‐ALL). Unbiased bioinformatics analysis enabled the authors to identify 13 T cell clusters in the patients based on their molecular properties. All 11 major T cell subsets in healthy individuals are found in the patients with B‐ALL, with the counterparts in the patients universally showing more activated characteristics. Two exhausted T cell populations, characterized by up‐regulation of TIGIT, PDCD1, HLADRA, LAG3, and CTLA4 are specifically discovered in B‐ALL patients. Of note, these exhausted T cells possess remarkable heterogeneity, and ten sub‐clusters are further identified, which are characterized by different cell cycle phases, naïve states, and GNLY (coding granulysin) expression. Coupled with single‐cell T cell receptor repertoire profiling, diverse originations of the exhausted T cells in B‐ALL are suggested, and clonally expanded exhausted T cells are likely to originate from CD8+ effector memory/terminal effector cells. Together, these data provide for the first‐time valuable insights for understanding exhausted T cell populations in leukemia. Single‐cell RNA sequencing analyses reveal common activation across T cell subsets under B cell‐acute lymphoblastic leukemia. Exhausted T cells specifically exist in patients, showing remarkable heterogeneity in molecular characteristics and extensive diversity in clonal derivation. In this study, valuable insights are provided for deeply understanding exhausted T cell populations in leukemia.