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Tissue-resident memory T cell signatures from single-cell analysis associated with better melanoma prognosis.

ABSTRACT: Tissue-resident memory T cells (T_RM) are a specialized T cell population residing in peripheral tissues. The presence and potential impact of T_RM in the tumor immune microenvironment (TIME) remain to be elucidated. Here, we systematically investigated the relationship between T_RM and melanoma TIME based on multiple clinical single-cell RNA-seq datasets and developed signatures indicative of T_RM infiltration. T_RM infiltration is associated with longer overall survival and abundance of T cells, NK cells, M1 macrophages, and memory B cells in the TIME. A 22-gene T_RM-derived risk score was further developed to effectively classify patients into low- and high-risk categories, distinguishing overall survival and immune activation, particularly in T cell-mediated responses. Altogether, our analysis suggests that T_RM abundance is associated with melanoma TIME activation and patient survival, and the T_RM-based machine learning model can potentially predict prognosis in melanoma patients.

SUBMITTER: Jiang C

PROVIDER: S-EPMC10918229 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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Tissue-resident memory T cell signatures from single-cell analysis associated with better melanoma prognosis.

Jiang Chongming C Chao Cheng-Chi CC Li Jianrong J Ge Xin X Shen Aidan A Jucaud Vadim V Cheng Chao C Shen Xiling X

iScience 20240220 3

Tissue-resident memory T cells (TRM) are a specialized T cell population residing in peripheral tissues. The presence and potential impact of TRM in the tumor immune microenvironment (TIME) remain to be elucidated. Here, we systematically investigated the relationship between TRM and melanoma TIME based on multiple clinical single-cell RNA-seq datasets and developed signatures indicative of TRM infiltration. TRM infiltration is associated wi ...[more]

PMID: 38455971

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Project description:IntroductionThe 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.MethodsWe 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.ResultsUnbiased 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.ConclusionIn 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.

Dataset Information

Tissue-resident memory T cell signatures from single-cell analysis associated with better melanoma prognosis.

Publications

Tissue-resident memory T cell signatures from single-cell analysis associated with better melanoma prognosis.

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