Cytotoxic FCER1G+ innate-like T cells: new potential for tumour immunotherapy

Morrish, Emma; Ruland, Jürgen

doi:10.1038/s41392-022-01061-4

Cited by 10 publications

(6 citation statements)

References 4 publications

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“…It is worth noting the functions of these genes reported in existing literature. T-cell receptor (TCR)-positive and Fcer1g-expressing innate-like T-cells are known to exhibit high cytotoxic activity ( Morrish and Ruland, 2022 ). Additionally, FCER1G downregulation has been correlated with a loss of immunoregulatory cytotoxic activity in Cd56-CD16 + (adaptive) NK cells ( Forconi et al, 2020 ).…”

Section: Resultsmentioning

confidence: 99%

PAGER-scFGA: unveiling cell functions and molecular mechanisms in cell trajectories through single-cell functional genomics analysis

Huang,

Welner,

Chen

et al. 2024

Front. Bioinform.

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Background: Understanding how cells and tissues respond to stress factors and perturbations during disease processes is crucial for developing effective prevention, diagnosis, and treatment strategies. Single-cell RNA sequencing (scRNA-seq) enables high-resolution identification of cells and exploration of cell heterogeneity, shedding light on cell differentiation/maturation and functional differences. Recent advancements in multimodal sequencing technologies have focused on improving access to cell-specific subgroups for functional genomics analysis. To facilitate the functional annotation of cell groups and characterization of molecular mechanisms underlying cell trajectories, we introduce the Pathways, Annotated Gene Lists, and Gene Signatures Electronic Repository for Single-Cell Functional Genomics Analysis (PAGER-scFGA).Results: We have developed PAGER-scFGA, which integrates cell functional annotations and gene-set enrichment analysis into popular single-cell analysis pipelines such as Scanpy. Using differentially expressed genes (DEGs) from pairwise cell clusters, PAGER-scFGA infers cell functions through the enrichment of potential cell-marker genesets. Moreover, PAGER-scFGA provides pathways, annotated gene lists, and gene signatures (PAGs) enriched in specific cell subsets with tissue compositions and continuous transitions along cell trajectories. Additionally, PAGER-scFGA enables the construction of a gene subcellular map based on DEGs and allows examination of the gene functional compartments (GFCs) underlying cell maturation/differentiation. In a real-world case study of mouse natural killer (mNK) cells, PAGER-scFGA revealed two major stages of natural killer (NK) cells and three trajectories from the precursor stage to NK T-like mature stage within blood, spleen, and bone marrow tissues. As the trajectories progress to later stages, the DEGs exhibit greater divergence and variability. However, the DEGs in different trajectories still interact within a network during NK cell maturation. Notably, PAGER-scFGA unveiled cell cytotoxicity, exocytosis, and the response to interleukin (IL) signaling pathways and associated network models during the progression from precursor NK cells to mature NK cells.Conclusion: PAGER-scFGA enables in-depth exploration of functional insights and presents a comprehensive knowledge map of gene networks and GFCs, which can be utilized for future studies and hypothesis generation. It is expected to become an indispensable tool for inferring cell functions and detecting molecular mechanisms within cell trajectories in single-cell studies. The web app (accessible at https://au-singlecell.streamlit.app/) is publicly available.

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Section: Resultsmentioning

confidence: 99%

PAGER-scFGA: unveiling cell functions and molecular mechanisms in cell trajectories through single-cell functional genomics analysis

Huang,

Welner,

Chen

et al. 2024

Front. Bioinform.

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“…2A). In addition, cluster 26 speci cally expressed FCER1G, a marker of an innate-like phenotype 37 . Cluster 24 resembled an exhausted progenitor phenotype based on CD7, TOX, and to some extent TCF7, but not CD27 expression.…”

Section: Identi Cation Of the Major Single-cell Clusters By Scrna-seqmentioning

confidence: 99%

A single-cell transcriptomic study reveals immune suppressive cancer cell-immune cell interactions in the triple negative canine breast cancers

Kim,

Borcherding,

Song

et al. 2023

Preprint

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Clinical trials show promising outcomes for dogs with advanced solid tumors following treatment with immune checkpoint inhibitors (ICIs). Triple-negative breast cancer (TNBC) is very aggressive with very low response rates to ICIs. No study defines how canine TNBC interacts with the immune system within the tumor microenvironment, which is investigated in this study at the single cell level. Single cell RNA sequencing (scRNA-seq) datasets, including 6 groups of 30 dogs, were subject to integrated bioinformatic analysis. Immune modulatory TNBC subsets were identified by functional enrichment with immune-suppressive gene sets, including anti-inflammatory and M2-like macrophages. Key genes and immune-suppressive signaling pathways for TNBC included angiogenesis and leukocyte chemotaxis. Interactome analysis identified significant interactions between distinct subsets of cancer cells and effector T cells, suggesting T cell suppression. This is the first study to define immune-suppressive cancer cell subsets at the single-cell level, revealing potential mechanisms by which TNBC induces immune evasion in dogs.

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“…The seminal work by Chou and colleagues has shed light on the unique attributes of this population, revealing heightened cytotoxicity, resilience against exhaustion, and a particularly noteworthy enhancement in tumor-homing capacity when compared to conventional cytotoxic (aka "killer") T cells [213]. These cytotoxic ILT cells were detected for the first time in murine prostate and human colorectal cancer tissues characterized by high NK1.1 expression [213,218].…”

Section: Hybrid Cells or New Immune Cells "Soldier"mentioning

confidence: 99%

“…Separate αβ TCRs implied distinct origins for CD8 + PD1 + and ILTCKs. Transcriptional profiles revealed antigen-related genes in ILTCK progenitors, suggesting autoantigen-driven selection, with Fcer1g emerging as a lineage-defining marker for ILTCK, already upregulated in thymic progenitors and expressed in differentiated and activated tumor-infiltrating ab ILTCKs, but not in CD8 + PD1 + T cells (Figure 4) [212,218].…”

Section: Hybrid Cells or New Immune Cells "Soldier"mentioning

confidence: 99%

“…The ILTCKs are produced from specific thymic progenitors succeeding the initial interaction with cognate antigens and were constantly replenished by thymic progenitors during tumor growth. They generally react to the unmutated self-antigens [218]. IL-15 produced by cancer cells is a major driver for expansion and effector differentiation of intertumoral ILTCKs (Figure 4).…”

Section: Hybrid Cells or New Immune Cells "Soldier"mentioning

confidence: 99%

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Small Molecule Targeting Immune Cells: A Novel Approach for Cancer Treatment

Singh,

Barik,

Arukha

et al. 2023

Biomedicines

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Conventional and cancer immunotherapies encompass diverse strategies to address various cancer types and stages. However, combining these approaches often encounters limitations such as non-specific targeting, resistance development, and high toxicity, leading to suboptimal outcomes in many cancers. The tumor microenvironment (TME) is orchestrated by intricate interactions between immune and non-immune cells dictating tumor progression. An innovative avenue in cancer therapy involves leveraging small molecules to influence a spectrum of resistant cell populations within the TME. Recent discoveries have unveiled a phenotypically diverse cohort of innate-like T (ILT) cells and tumor hybrid cells (HCs) exhibiting novel characteristics, including augmented proliferation, migration, resistance to exhaustion, evasion of immunosurveillance, reduced apoptosis, drug resistance, and heightened metastasis frequency. Leveraging small-molecule immunomodulators to target these immune players presents an exciting frontier in developing novel tumor immunotherapies. Moreover, combining small molecule modulators with immunotherapy can synergistically enhance the inhibitory impact on tumor progression by empowering the immune system to meticulously fine-tune responses within the TME, bolstering its capacity to recognize and eliminate cancer cells. This review outlines strategies involving small molecules that modify immune cells within the TME, potentially revolutionizing therapeutic interventions and enhancing the anti-tumor response.

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Cytotoxic FCER1G+ innate-like T cells: new potential for tumour immunotherapy

Cited by 10 publications

References 4 publications

PAGER-scFGA: unveiling cell functions and molecular mechanisms in cell trajectories through single-cell functional genomics analysis

PAGER-scFGA: unveiling cell functions and molecular mechanisms in cell trajectories through single-cell functional genomics analysis

A single-cell transcriptomic study reveals immune suppressive cancer cell-immune cell interactions in the triple negative canine breast cancers

Small Molecule Targeting Immune Cells: A Novel Approach for Cancer Treatment

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