Single-Cell RNA-Seq of T Cells in B-ALL Patients Reveals an Exhausted Subset with Remarkable Heterogeneity.
Adv Sci (Weinh)
; 8(19): e2101447, 2021 10.
Article
in En
| MEDLINE
| ID: mdl-34365737
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
T-Lymphocyte Subsets
/
Lymphocytes, Tumor-Infiltrating
/
Precursor Cell Lymphoblastic Leukemia-Lymphoma
/
RNA-Seq
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Adv Sci (Weinh)
Year:
2021
Document type:
Article