ABSTRACT
Mucosal-associated invariant T (MAIT) cells constitute one of the most numerous unconventional T cell subsets, and are characterized by rapid release of Th1- and Th17-associated cytokines and increased cytotoxic functions following activation. MAIT cells accumulate in tumor tissue but show an exhausted phenotype. Here, we investigated if immune checkpoint blockade (ICB) with antibodies to PD-1 or PD-L1 affects the function of circulating MAIT cells from non-small cell lung cancer patients. ICB increased the proliferation and co-expression of the activation markers HLA-DR and CD38 on MAIT cells in most patients after the first treatment cycle, irrespective of treatment outcome. Furthermore, production of cytokines, especially TNF and IL-2, also increased after treatment, as did MAIT cell polyfunctionality. These results indicate that MAIT cells respond to ICB, and that MAIT cell reinvigoration may contribute to tumor regression in patients undergoing immune checkpoint therapy.
Abbreviations
5-OP-RU | = | 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil |
GrB | = | Granzyme B |
ICB | = | Immune checkpoint blockade |
MAIT cell | = | Mucosal-associated invariant T cell |
MR1 | = | major histocompatibility complex class I-related protein 1 |
NSCLC | = | non-small cell lung cancer |
PD-1 | = | programmed cell death 1 |
PD-L1 | = | PD-ligand 1 |
TCR | = | T cell receptor |
Data availability statement
The authors confirm that the data supporting the findings of this study are available within the article and its supplementary materials.
Disclosure statement
M Quiding Järbrink has received consultancy fees from Biomunex Pharmaceuticals.
Acknowledgments
We would like to thank all patients for their participation in this study. Study nurse Christina Krångh Turesson is also gratefully acknowledged for her help.
Tetramers of MR1 were kindly provided by the NIH tetramer core facility. The MR1 tetramer technology was developed jointly by Dr. James McCluskey, Dr. Jamie Rossjohn, and Dr. David Fairlie. The material was produced by the NIH Tetramer Core Facility and permitted to be distributed by the University of Melbourne.
Supplementary material
Supplemental data for this article can be accessed online at https://doi.org/10.1080/2162402X.2024.2312631