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

Gherardin, NA; Loh, L; Admojo, L; Davenport, AJ; Richardson, K; Rogers, A; Darcy, PK; Jenkins, MR; Prince, HM; Harrison, SJ; Quach, H; Fairlie, DP; Kedzierska, K; McCluskey, J; Uldrich, AP; Neeson, PJ; Ritchie, DS; Godfrey, DI

Author(s): Gherardin, NA; Loh, L; Admojo, L; Davenport, AJ; Richardson, K; Rogers, A; Darcy, PK; Jenkins, MR; Prince, HM; Harrison, SJ; Quach, H; Fairlie, DP; Kedzierska, K; McCluskey, J; Uldrich, AP; Neeson, PJ; Ritchie, DS; Godfrey, DI;
Details: Publication Year 2018-03-07,Volume 8,Issue #1,Page 4159
Journal Title: Scientific Reports
Publication Type: Journal Article
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 IFNgamma production and CD27 expression, suggesting an exhausted phenotype, although IFNgamma-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.
Publisher: Springer Nature
Research Division(s): Immunology
PubMed ID: 29515123
Publisher's Version: https://doi.org/10.1038/s41598-018-22130-1
Open Access at Publisher's Site: https://doi.org/10.1038/s41598-018-22130-1
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2018-03-19 10:02:34

Last Modified: 2018-03-19 10:23:14