Single-cell profiling of T cells uncovers a tissue-resident memory-like T-cell subset associated with bidirectional prognosis for B-cell acute lymphoblastic leukemia

• Published in: Frontiers in immunology 2022-12, Vol.13, p.957436
• Main Authors: Lai, Wenpu, Wang, Xiaofang, Liu, Lian, Xu, Ling, Mao, Lipeng, Tan, Jiaxiong, Zha, Xianfeng, Zhan, Huien, Lei, Wen, Lan, Yu, Chen, Guobing, Li, Yangqiu, Luo, Oscar Junhong
• Format: Article
• Language: English
• Subjects: gene expression profiling; hematologic neoplasms; Humans; immunity; Immunologic Memory; Immunology; Immunotherapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prognosis; T-Lymphocyte Subsets; T-lymphocytes
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2022.957436

The character and composition of leukemia-related T cells are closely related to the treatment response and prognosis for patients. Though B cell-acute lymphoblastic leukemia (B-ALL) patients have benefited from immune-based approaches, such as chimeric antigen receptor T cells therapy, some of them still end with poor prognosis, especially for adult patients. Therefore, deep understanding of the developmental relationship between T cell subtypes in relation to B-ALL patient prognosis is urgently needed. We analyzed the peripheral blood T cell single-cell RNA sequencing data of three B-ALL patients, using data from 11 healthy individuals as controls. In total, 16,143 and 53,701 T cells from B-ALL patients and healthy adults, respectively, were objectively analyzed for detailed delineation of 13 distinct T cell clusters. Cluster-specific genes were used as marker genes to annotate each T cell subtype. Unbiased analysis enabled the discovery of circulating CD103+ T cell (CD3+CD103+MKI67+), also defined as tissue-resident memory-like T (Trm-like) cell, populations were elevated in B-ALL patients, which expressed high level of cell proliferation and exhaustion related genes. In addition, cell fate trajectory analysis showed these Trm-like cells, which shared T-cell receptor (TCR) clonotypes with exhausted T (Tex) cells and effector T (Teff) cells, were supposed to transition into Teff cells; however, mainly transformed into Tex cells in leukemia environment. More importantly, Trm-like cells transformation into Teff cells and Tex cells potentially led to favorable or poor prognosis for B-ALL patients, respectively. In sum, a circulating Trm-like cell subset with high level expression of cell proliferation and exhaustion related genes was elevated in B-ALL patients. The bidirectional developmental potential of these T cells into Teff or Tex is closely associated with favorable or poor prognosis, respectively. Together, our study provided a unique insight of alteration of leukemia related T cells, also showed a potential immunotherapy direction and prognosis assessment model for B-ALL patients.