| Literature DB >> 34362900 |
Dale I Godfrey1,2, Paul A Beavis3,4,5, Phillip K Darcy6,7,8,9, Emma V Petley10,11, Hui-Fern Koay12,13, Melissa A Henderson10,11, Kevin Sek10,11, Kirsten L Todd10,11, Simon P Keam10,11,14, Junyun Lai10,11, Imran G House10,11, Jasmine Li10,11, Magnus Zethoven11,15, Amanda X Y Chen10,11, Amanda J Oliver10,11, Jessica Michie10,11, Andrew J Freeman10,11, Lauren Giuffrida10,11, Jack D Chan10,11, Angela Pizzolla10,11, Jeffrey Y W Mak16,17, Timothy R McCulloch18, Fernando Souza-Fonseca-Guimaraes18, Conor J Kearney10,11, Rosemary Millen10,11, Robert G Ramsay10,11, Nicholas D Huntington19,20,21, James McCluskey12, Jane Oliaro10,11,22, David P Fairlie16,17, Paul J Neeson10,11.
Abstract
The function of MR1-restricted mucosal-associated invariant T (MAIT) cells in tumor immunity is unclear. Here we show that MAIT cell-deficient mice have enhanced NK cell-dependent control of metastatic B16F10 tumor growth relative to control mice. Analyses of this interplay in human tumor samples reveal that high expression of a MAIT cell gene signature negatively impacts the prognostic significance of NK cells. Paradoxically, pre-pulsing tumors with MAIT cell antigens, or activating MAIT cells in vivo, enhances anti-tumor immunity in B16F10 and E0771 mouse tumor models, including in the context of established metastasis. These effects are associated with enhanced NK cell responses and increased expression of both IFN-γ-dependent and inflammatory genes in NK cells. Importantly, activated human MAIT cells also promote the function of NK cells isolated from patient tumor samples. Our results thus describe an activation-dependent, MAIT cell-mediated regulation of NK cells, and suggest a potential therapeutic avenue for cancer treatment.Entities:
Year: 2021 PMID： 34362900 DOI： 10.1038/s41467-021-25009-4
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919