Landscape of T Cells in NK-AML(M4/M5) Revealed by Single-Cell Sequencing

Wu, Wenqi; Liang, Xiaolin; Li, Huiqun; Huang, Xiaoke; Wan, Chengyao; Xie, Qiongni; Liu, Zhenfang

doi:10.1002/jlb.5a0721-396rr

Cited by 6 publications

(8 citation statements)

References 54 publications

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“…Several of these are known to be responsible for maintaining the stem-like state of the progenitor exhausted CD8 T cells. LYL1 is responsible for stem / progenitor state and self-renewal in thymocytes and T cells [31, 32, 33]. BCL11A slows differentiation of T cells to maintain self-renewal [34].…”

Section: Resultsmentioning

confidence: 99%

Identification of Cellular Interactions in the Tumor Immune Microenvironment Underlying CD8 T Cell Exhaustion

Klocke,

Moran,

Adey

et al. 2023

Preprint

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While immune checkpoint inhibitors show success in treating a subset of patients with certain late-stage cancers, these treatments fail in many other patients as a result of mechanisms that have yet to be fully characterized. The process of CD8 T cell exhaustion, by which T cells become dysfunctional in response to prolonged antigen exposure, has been implicated in immunotherapy resistance. Single-cell RNA sequencing (scRNA-seq) produces an abundance of data to analyze this process; however, due to the complexity of the process, contributions of other cell types to a process within a single cell type cannot be simply inferred. We constructed an analysis framework to first rank human skin tumor samples by degree of exhaustion in tumor-infiltrating CD8 T cells and then identify immune cell type-specific gene-regulatory network patterns significantly associated with T cell exhaustion. Using this framework, we further analyzed scRNA-seq data from human tumor and chronic viral infection samples to compare the T cell exhaustion process between these two contexts. In doing so, we identified transcription factor activity in the macrophages of both tissue types associated with this process. Our framework can be applied beyond the tumor immune microenvironment to any system involving cell-cell communication, facilitating insights into key biological processes that underpin the effective treatment of cancer and other complicated diseases.

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Section: Resultsmentioning

confidence: 99%

Identification of Cellular Interactions in the Tumor Immune Microenvironment Underlying CD8 T Cell Exhaustion

Klocke,

Moran,

Adey

et al. 2023

Preprint

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“…Contradictive to previous findings, a case-report study of 5 AML patients reported quite opposite findings in terms of accumulation of MAIT cells in bone marrow. 37 Finally, tumour cells might possess the capacity to stimulate MAIT cells, leading to their activation, exhaustion and their eventual depletion. This hypothesis is supported by the fact that myeloma cell lines do express MR-1 on their surface membrane and therefore can activate MAIT cells.…”

Section: Discussionmentioning

confidence: 99%

“…Likewise, flow cytometric analysis of nine suspensions of lymph nodes from patients both with haematological diseases and patients with no histologically confirmed malignancy did not show significant accumulation of MAIT cells. Contradictive to previous findings, a case‐report study of 5 AML patients reported quite opposite findings in terms of accumulation of MAIT cells in bone marrow 37 …”

Section: Discussionmentioning

confidence: 99%

Systematic analysis of mucosal‐associated invariant T cells in haematological malignancies

Bacova,

Cierny,

Nemcekova

et al. 2024

Scand J Immunol

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Mucosal‐associated invariant T‐cells (MAIT) are unconventional T‐cells with cytotoxic and pro‐inflammatory properties. Previous research has reported contradictory findings on their role in cancerogenesis with data being even scarcer in haematological malignancies. Here, we report the results of a systematic analysis of MAIT cells in treatment‐naïve patients with a broad range of haematological malignancies. We analysed peripheral blood of 204 patients and 50 healthy subjects. The pool of haematological patients had a statistically significant lower both the absolute value (median values, 0.01 × 109/L vs. 0.05 × 109/L) of MAIT cells and their percentage (median values 0.94% vs. 2.56%) among T‐cells compared to the control group. Separate analysis showed that the decrease in the absolute number of MAIT cells is significant in patients with acute myeloid leukaemia, myeloproliferative neoplasms, plasma cell myeloma, B‐cell non‐Hodgkin lymphomas, otherwise not specified, diffuse large B‐cell lymphoma, follicular lymphoma, mantle cell lymphoma, marginal zone lymphoma compared to the control population. Furthermore, in haematological malignancies, MAIT cells overexpress PD‐1 (average values, 51.7% vs. 6.7%), HLA‐DR (average values, 40.2% vs. 7%), CD38 (average values, 25.9% vs. 4.9%) and CD69 (average values, 40.2% vs. 9.2%). Similar results were obtained when comparing patients with individual malignancies to the control population. Our data show that the depletion of circulating MAIT cells is a common observation in a broad spectrum of haematological malignancies. In addition to their reduced numbers, MAIT cells acquire an activated/exhausted phenotype.

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“…Interestingly, a recent article ( 14 ) described the clonal expansion of MAIT cells in the BM of patients with a specific subtype of AML (NK AML M4/M5). Intriguingly, the only patient not achieving complete remission showed a larger MAIT cell infiltration and expression of a specific gene transcription signature.…”

Section: Mait Cells In Hematologic Malignanciesmentioning

confidence: 99%

Mucosal-associated invariant T cells in hematological malignancies: Current knowledge, pending questions

Treiner

2023

Front. Immunol.

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Non-classical HLA restricted T cell subsets such as γδ T and NK-T cells are showing promises for immune-based therapy of hematological malignancies. Mucosal-Associated Invariant T cells (MAIT) belong to this family of innate-like T cell subsets and are the focus of many studies on infectious diseases, owing to their unusual recognition of bacterial/fungal metabolites. Their ability to produce type 1 cytokines (IFNγ, TNFα) as well as cytotoxic effector molecules endows them with potential anti-tumor functions. However, their contribution to tumor surveillance in solid cancers is unclear, and only few studies have specifically focused on MAIT cells in blood cancers. In this review, we wish to recapitulate our current knowledge on MAIT cells biology in hematological neoplasms, at diagnosis and/or during treatment, as well as tentative approaches to target them as therapeutic tools. We also wish to take this opportunity to briefly elaborate on what we think are important question to address in this field, as well as potential limitations to overcome in order to make MAIT cells the basis of future, novel therapies for hematological cancers.

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Landscape of T Cells in NK-AML(M4/M5) Revealed by Single-Cell Sequencing

Cited by 6 publications

References 54 publications

Identification of Cellular Interactions in the Tumor Immune Microenvironment Underlying CD8 T Cell Exhaustion

Identification of Cellular Interactions in the Tumor Immune Microenvironment Underlying CD8 T Cell Exhaustion

Systematic analysis of mucosal‐associated invariant T cells in haematological malignancies

Mucosal-associated invariant T cells in hematological malignancies: Current knowledge, pending questions

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