Open AccessSingle‐Cell RNA‐Seq of T Cells in B‐ALL Patients Reveals an Exhausted Subset with Remarkable Heterogeneity
Author(s) -
Wang Xiaofang,
Chen Yanjuan,
Li Zongcheng,
Huang Bingyan,
Xu Ling,
Lai Jing,
Lu Yuhong,
Zha Xianfeng,
Liu Bing,
Lan Yu,
Li Yangqiu
Publication year - 2021
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.202101447
Subject(s) - tigit , biology , cd8 , effector , t cell , immunophenotyping , granulysin , b cell , cytotoxic t cell , cell , immunology , computational biology , flow cytometry , genetics , antigen , immune system , antibody , perforin , in vitro
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.