Abstract:
:Mucosa-associated invariant T (MAIT) cells are unconventional, innate-like T lymphocytes that recognize vitamin B metabolites of microbial origin among other antigens displayed by the monomorphic molecule MHC class I-related protein 1 (MR1). Abundant in human tissues, reactive to local inflammatory cues, and endowed with immunomodulatory and cytolytic functions, MAIT cells are likely to play key roles in human malignancies. They accumulate in various tumor microenvironments (TMEs) where they often lose some of their functional capacities. However, the potential roles of MAIT cells in anticancer immunity or cancer progression and their significance in shaping clinical outcomes remain largely unknown. In this study, we analyzed publicly available bulk and single-cell tumor transcriptomic datasets to investigate the tissue distribution, phenotype, and prognostic significance of MAIT cells across several human cancers. We found that expanded MAIT cell clonotypes were often shared between the blood, tumor tissue and adjacent healthy tissue of patients with colorectal, hepatocellular, and non-small cell lung carcinomas. Gene expression comparisons between tumor-infiltrating and healthy tissue MAIT cells revealed the presence of activation and/or exhaustion programs within the TMEs of primary hepatocellular and colorectal carcinomas. Interestingly, in basal and squamous cell carcinomas of the skin, programmed cell death-1 (PD-1) blockade upregulated the expression of several effector genes in tumor-infiltrating MAIT cells. We derived a signature comprising stable and specific MAIT cell gene markers across several tissue compartments and cancer types. By applying this signature to estimate MAIT cell abundance in pan-cancer gene expression data, we demonstrate that a heavier intratumoral MAIT cell presence is positively correlated with a favorable prognosis in esophageal carcinoma but predicts poor overall survival in colorectal and squamous cell lung carcinomas. Finally, in colorectal carcinoma and four other cancer types, we found a positive correlation between MR1 expression and estimated MAIT cell abundance. 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.
journal_name
Front Immunoljournal_title
Frontiers in immunologyauthors
Yao T,Shooshtari P,Haeryfar SMMdoi
10.3389/fimmu.2020.01691subject
Has Abstractpub_date
2020-07-31 00:00:00pages
1691issn
1664-3224journal_volume
11pub_type
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journal_title:Frontiers in immunology
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abstract::[This corrects the article DOI: 10.3389/fimmu.2020.00367.]. ...
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abstract::The mechanism by which antigen binding to the T cell antigen receptor (TCR) generates intracellular signaling, a process termed TCR triggering, is incompletely understood. A large body of experimental evidence has implicated multiple biophysical/biochemical effects and multiple molecules in the process of TCR triggeri...
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doi:10.3389/fimmu.2011.00091
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pub_type: 杂志文章,评审
doi:10.3389/fimmu.2018.02653
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doi:10.3389/fimmu.2019.00280
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pub_type: 杂志文章,评审
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doi:10.3389/fimmu.2020.599936
更新日期:2020-12-14 00:00:00
abstract::The approval of the first two monoclonal antibodies targeting CD38 (daratumumab) and SLAMF7 (elotuzumab) in late 2015 for treating relapsed and refractory multiple myeloma (RRMM) was a critical advance for immunotherapies for multiple myeloma (MM). Importantly, the outcome of patients continues to improve with the inc...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2018.01821
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abstract::Natural killer (NK) cells play an important role in the containment of HIV replication during primary infection, though their functions are impaired during chronic HIV infection. Infants experience more rapid HIV disease progression than adults, but contributions of infant NK cells to containing HIV infection are unkn...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2012.00399
更新日期:2012-12-31 00:00:00
abstract::DiGeorge syndrome is an immunodeficiency characterized by thymic dysplasia resulting in T cell lymphopenia. Most patients suffer from increased susceptibility to infections and heightened prevalence of autoimmune disorders, such as autoimmune thrombocytopenia. B cells in DiGeorge syndrome show impaired maturation, wit...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.01730
更新日期:2018-07-23 00:00:00
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journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2017.01494
更新日期:2017-11-09 00:00:00
abstract::Although NGS technologies fuel advances in high-throughput HLA genotyping methods for identification and classification of HLA genes to assist with precision medicine efforts in disease and transplantation, the efficiency of these methods are impeded by the absence of adequately-characterized high-frequency HLA allele...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.02294
更新日期:2018-10-04 00:00:00
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journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.02531
更新日期:2018-11-02 00:00:00
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journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2019.02751
更新日期:2019-12-11 00:00:00
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journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.00797
更新日期:2020-05-05 00:00:00
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journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2017.00546
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pub_type: 杂志文章,评审
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更新日期:2017-09-21 00:00:00
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journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.02443
更新日期:2019-10-18 00:00:00
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journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2018.00579
更新日期:2018-04-05 00:00:00
abstract::Mycobacteria display pro- and anti-inflammatory effects in human and experimental pathology. We show here that both effects are mediated by Toll-like receptor 2 (Tlr2), by exploiting a previously characterized Tlr2 variant (Met82Ile). Tlr2 82ile promoted self-specific proinflammatory polarization as well as expansion ...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2016.00191
更新日期:2016-05-24 00:00:00
abstract::This study first systematically analyzed the constituents of an albino mutant strain of Auricularia cornea (AU). After 8 weeks of continuous treatment with metformin (Met) (0.1 g/kg) and AU (0.1 and 0.4 g/kg), db/db mice showed hypoglycemic functioning, indicated by reduced bodyweight, food intake, plasma glucose, ser...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.01039
更新日期:2019-05-08 00:00:00
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journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2020.00874
更新日期:2020-05-19 00:00:00
abstract::Background: Characterization of the intracellular biochemical processes that regulate the generation and maintenance of effector and memory CD8+ T-cells from naïve precursors is essential for our understanding of adaptive immune responses and the development of immunotherapies. However, the metabolic determinants of a...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.02736
更新日期:2018-12-21 00:00:00
abstract::Lyme disease (Borrelia burgdorferi infection) is increasingly recognized as a significant source of morbidity worldwide. Here, we show that blood plasmablasts and CD27- memory B cells are elevated in untreated Lyme disease, with higher plasmablast levels associated with more rapid resolution of clinical symptoms. Stro...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.01634
更新日期:2018-07-18 00:00:00