Leveraging Public Single-Cell and Bulk Transcriptomic Datasets to Delineate MAIT Cell Roles and Phenotypic Characteristics in Human Malignancies

Yao, Tony; Shooshtari, Parisa; Haeryfar, S. M. Mansour

doi:10.3389/fimmu.2020.01691

Cited by 32 publications

(38 citation statements)

References 103 publications

(186 reference statements)

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“…A recent CRC study noted that the tumor-residing MAIT cell exhausted phenotype is characterized by TCR-induced CD39 expression [24] (Figure 3). This is consistent with other work showing that chronic TCR stimulation on intra-tumoral MAIT cells leads to decreased responsiveness and upregulation of PD-1 and exhaustion markers CD39 and CXCL13, [79,80] (Figure 3), demonstrating tumor-infiltrating MAIT cell dysfunction associated with the TME. The mechanisms resulting in MAIT cell activation within the TME are still not fully understood.…”

Section: Mucosal-associated Cancerssupporting

confidence: 93%

“…Analyses of data from The Cancer Genome Atlas (TCGA) associated high MAIT cell gene signatures with improved overall survival and progression free survival in esophageal cancer patients [80]. However, this same analysis found worse overall survival in patients diagnosed with CRC and lung squamous cell carcinoma with increased MAIT cell signatures [80].…”

Section: Mucosal-associated Cancersmentioning

confidence: 97%

“…Other studies of squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) observed that tumor-residing MAIT cells upregulated expression of IFN-γ, GZM K, GZM A and GZM M following PD-1 blockade [80]. Additionally, higher MAIT cell proportions were recently found to correlate with better responses to anti-PD-1 immunotherapy, with MAIT cells from responders having a greater cytotoxic function [28].…”

Section: Immunotherapymentioning

confidence: 98%

“…Links have also been made between microbiome composition, antibiotic use, and the severity of esophageal cancers, suggesting that bacteria inhabiting the esophagus could impact the MAIT cell response to esophageal cancer cells [82]. Analyses of data from The Cancer Genome Atlas (TCGA) associated high MAIT cell gene signatures with improved overall survival and progression free survival in esophageal cancer patients [80]. However, this same analysis found worse overall survival in patients diagnosed with CRC and lung squamous cell carcinoma with increased MAIT cell signatures [80].…”

Section: Mucosal-associated Cancersmentioning

confidence: 99%

“…Hepatocellular carcinomas (HCC) generally exhibit decreased MAIT cell frequencies compared to healthy adjacent liver tissue [11,19,80], with corresponding decreases in peripheral circulation [19,80], contrary to the mucosal cancers discussed above (Table 1). A possible mechanism accounting for this observation could be via the migratory receptors CCR9, CCR6, and CXCR6 which are significantly downregulated on MAIT cells in the circulation and TME in patients with HCC (Figure 1).…”

Section: Hepatic Cancersmentioning

confidence: 99%

See 4 more Smart Citations

MAIT Cells: Partners or Enemies in Cancer Immunotherapy?

Cogswell

Gapin

Tobin

et al. 2021

Cancers

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A recent boom in mucosal-associated invariant T (MAIT) cell research has identified relationships between MAIT cell abundance, function, and clinical outcomes in various malignancies. As they express a variety of immune checkpoint receptors and ligands, and possess strong cytotoxic functions, MAIT cells are an attractive new subject in the field of tumor immunology. MAIT cells are a class of innate-like T cells that express a semi-invariant T cell antigen receptor (TCR) that recognizes microbially derived non-peptide antigens presented by the non-polymorphic MHC class-1 like molecule, MR1. In this review, we outline the current (and often contradictory) evidence exploring MAIT cell biology and how MAIT cells impact clinical outcomes in different human cancers, as well as what role they may have in cancer immunotherapy.

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Section: Mucosal-associated Cancerssupporting

confidence: 93%

Section: Mucosal-associated Cancersmentioning

confidence: 97%

Section: Immunotherapymentioning

confidence: 98%

Section: Mucosal-associated Cancersmentioning

confidence: 99%

Section: Hepatic Cancersmentioning

confidence: 99%

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MAIT Cells: Partners or Enemies in Cancer Immunotherapy?

Cogswell

Gapin

Tobin

et al. 2021

Cancers

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T cell landscape and dynamics in immunoglobulin light chain amyloidosis before and after daratumumab‐based therapy

Wang

Zhao

et al. 2021

Clinical & Translational Med

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Amyloid light‐chain (AL) is characterized by the presence of small, poorly proliferating plasma cell clones with the production and deposition of light chains into tissues. T cell changes within the tumour microenvironment in AL are poorly understood. By sequencing at a single‐cell level of CD3 + T cells purified from bone marrow (BM) and blood of newly diagnosed AL patients before and after a combination of daratumumab with cyclophosphamide, bortezomib, and dexamethasone (Dara‐BCD), we analysed the transcriptomic features of T cells and found an expansion, activation and type I cytokine upregulation in BM and circulating T cells after the treatment. More prominent changes were shown in CD8 + T cells. In particular, we found the presence of CD8 + BM resident memory T cells (T RM ) with high expression of inhibitory molecules in AL patients at diagnosis. After Dara‐BCD, these T RM cells were quickly activated with downregulation of suppressive molecules and upregulation of IFNG expression. These data collectively demonstrate that Dara‐based therapy in patients with AL amyloidosis promotes anti‐tumour T cell responses. The similar transcriptomic features of BM and circulating T cells before and after therapy further provide a less invasive approach for molecular monitoring of T cell response in AL amyloidosis.

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Revealing the transcriptional heterogeneity of organ‐specific metastasis in human gastric cancer using single‐cell RNA Sequencing

Jiang

Yang

et al. 2022

Clinical & Translational Med

115

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Background Deciphering intra‐ and inter‐tumoural heterogeneity is essential for understanding the biology of gastric cancer (GC) and its metastasis and identifying effective therapeutic targets. However, the characteristics of different organ‐tropism metastases of GC are largely unknown. Methods Ten fresh human tissue samples from six patients, including primary tumour and adjacent non‐tumoural samples and six metastases from different organs or tissues (liver, peritoneum, ovary, lymph node) were evaluated using single‐cell RNA sequencing. Validation experiments were performed using histological assays and bulk transcriptomic datasets. Results Malignant epithelial subclusters associated with invasion features, intraperitoneal metastasis propensity, epithelial–mesenchymal transition‐induced tumour stem cell phenotypes, or dormancy‐like characteristics were discovered. High expression of the first three subcluster‐associated genes displayed worse overall survival than those with low expression in a GC cohort containing 407 samples. Immune and stromal cells exhibited cellular heterogeneity and created a pro‐tumoural and immunosuppressive microenvironment. Furthermore, a 20‐gene signature of lymph node‐derived exhausted CD8+ T cells was acquired to forecast lymph node metastasis and validated in GC cohorts. Additionally, although anti‐NKG2A (KLRC1) antibody have not been used to treat GC patients even in clinical trials, we uncovered not only malignant tumour cells but one endothelial subcluster, mucosal‐associated invariant T cells, T cell‐like B cells, plasmacytoid dendritic cells, macrophages, monocytes, and neutrophils may contribute to HLA‐E‐KLRC1/KLRC2 interaction with cytotoxic/exhausted CD8+ T cells and/or natural killer (NK) cells, suggesting novel clinical therapeutic opportunities in GC. Additionally, our findings suggested that PD‐1 expression in CD8+ T cells might predict clinical responses to PD‐1 blockade therapy in GC. Conclusions This study provided insights into heterogeneous microenvironment of GC primary tumours and organ‐specific metastases and provide support for precise diagnosis and treatment.

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Leveraging Public Single-Cell and Bulk Transcriptomic Datasets to Delineate MAIT Cell Roles and Phenotypic Characteristics in Human Malignancies

Abstract: Collectively, our findings indicate that MAIT cells serve important but diverse roles in human cancers. Our work provides useful models and resources that employ gene expression data platforms to enable future studies in the realm of MAIT cell biology.

Cited by 32 publications

References 103 publications

MAIT Cells: Partners or Enemies in Cancer Immunotherapy?

MAIT Cells: Partners or Enemies in Cancer Immunotherapy?

T cell landscape and dynamics in immunoglobulin light chain amyloidosis before and after daratumumab‐based therapy

Revealing the transcriptional heterogeneity of organ‐specific metastasis in human gastric cancer using single‐cell RNA Sequencing

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