Enumeration, functional responses and cytotoxic capacity of MAIT cells in newly diagnosed and relapsed multiple myeloma View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-12

AUTHORS

Nicholas A. Gherardin, Liyen Loh, Lorenztino Admojo, Alexander J. Davenport, Kelden Richardson, Amy Rogers, Phillip K. Darcy, Misty R. Jenkins, H. Miles Prince, Simon J. Harrison, Hang Quach, David P. Fairlie, Katherine Kedzierska, James McCluskey, Adam P. Uldrich, Paul J. Neeson, David S. Ritchie, Dale I. Godfrey

ABSTRACT

Mucosal-associated invariant T (MAIT) cells are T cells that recognise vitamin-B derivative Ag presented by the MHC-related-protein 1 (MR1) antigen-presenting molecule. While MAIT cells are highly abundant in humans, their role in tumour immunity remains unknown. Here we have analysed the frequency and function of MAIT cells in multiple myeloma (MM) patients. We show that MAIT cell frequency in blood is reduced compared to healthy adult donors, but comparable to elderly healthy control donors. Furthermore, there was no evidence that MAIT cells accumulated at the disease site (bone marrow) of these patients. Newly diagnosed MM patient MAIT cells had reduced IFNγ production and CD27 expression, suggesting an exhausted phenotype, although IFNγ-producing capacity is restored in relapsed/refractory patient samples. Moreover, immunomodulatory drugs Lenalidomide and Pomalidomide, indirectly inhibited MAIT cell activation. We further show that cell lines can be pulsed with vitamin-B derivative Ags and that these can be presented via MR1 to MAIT cells in vitro, to induce cytotoxic activity comparable to that of natural killer (NK) cells. Thus, MAIT cells are reduced in MM patients, which may contribute to disease in these individuals, and moreover, MAIT cells may represent new immunotherapeutic targets for treatment of MM and other malignancies. More... »

PAGES

4159

References to SciGraph publications

Journal

TITLE

Scientific Reports

ISSUE

1

VOLUME

8

From Grant

  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41598-018-22130-1

    DOI

    http://dx.doi.org/10.1038/s41598-018-22130-1

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1101298957

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/29515123


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