A GROUNDBREAKING study has identified a naturally occurring ligand derived from vitamin B6 that can activate immune cells to target tumours. The study explores how the major histocompatibility complex class I-related protein (MR1) presents pyridoxal, a form of vitamin B6, to T cells, specifically the 7.G5 TCR. This T cell receptor has a broad “pan-cancer” specificity, potentially paving the way for novel cancer immunotherapies.
MR1, typically known for presenting microbial metabolites to mucosal-associated invariant T (MAIT) cells, can also display non-microbial metabolites like vitamin B6 derivatives. Using advanced mass spectrometry, researchers discovered that both pyridoxal and its phosphate derivative, pyridoxal 5-phosphate, bind covalently to MR1 and activate T cells expressing the 7.G5 receptor. These T cells, which recognise cancerous cells, were shown to be particularly responsive to the presentation of pyridoxal, suggesting a link between increased vitamin B6 metabolism in tumours and enhanced immune recognition.
The study also found that MR1’s ability to accommodate different vitamin scaffolds in its binding site may explain its broad recognition capacity. The findings highlight a potential mechanism by which tumours, through altered vitamin B6 metabolism, could be targeted more effectively by immune cells. This research opens new possibilities for developing therapies that leverage the immune system to fight a range of cancers.
Reference
McInerney M et al. MR1 presents vitamin B6–related compounds for recognition by MR1-reactive T cells. 2024;121(49)e2414792121.
