Single‐Cell RNA‐Seq of T Cells in B‐ALL Patients Reveals an Exhausted Subset with Remarkable Heterogeneity. Issue 19 (8th August 2021)

• Record Type: Journal Article
• Authors: Wang, Xiaofang; Chen, Yanjuan; Li, Zongcheng; Huang, Bingyan; Xu, Ling; Lai, Jing; Lu, Yuhong; Zha, Xianfeng; Liu, Bing; Lan, Yu; Li, Yangqiu
• Is Part Of: Advanced science. Volume 8:Issue 19(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-08-08
• Subjects: B cell‐acute lymphoblastic leukemia -- heterogeneity -- single‐cell RNA sequencing -- T cells; Science -- Periodicals; 505
• DOI: 10.1002/advs.202101447
• Languages: English
• ISSNs: 2198-3844

Abstract

Abstract: 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. Abstract : 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.