Effective immunity hinges on the ability to sense infection and cellular transformation. In humans, there is a specialised molecule on the surface of cells termed MR1. MR1 allows sensing of certain small molecule metabolites derived from cellular and microbial sources; however, the breadth of metabolite sensing is unclear.
Published in PNAS, researchers at the Monash University Biomedicine Discovery Institute have identified a form of Vitamin B6 bound to MR1 as a means of engaging tumour-reactive immune cells. The work involved an international collaborative team co-led by researchers from the University of Melbourne.
According to Dr Illing, "Our findings suggest that Vitamin B6 molecules displayed by MR1 represent a means for the immune system to detect altered cellular metabolism/metabolite levels, that may distinguish cancer cells," she said.
"Identification of small molecules/metabolites able to activate immune cells with cancer reactivity is a key step in understanding how small molecule sensing might contribute to anti-cancer immunity."
Central to this study were the unbiased mass spectrometry analysis of small molecules bound to MR1, the structural resolution of the interactions between MR1 and Vitamin B6, and immunological assays performed by lead authors Dr Mitchell McInerney and Dr Wael Awad at Monash Biomedicine Discovery Institute, and Dr Michael Souter and Mr Yang Kang at the University of Melbourne, Peter Doherty Institute.
While it's not yet clear if the Vitamin B6 molecule can be utilised in therapeutics, "understanding the breadth of MR1 mediated immunity has the capacity to illuminate routes for therapeutic intervention," Dr Illing said.
An important aspect of the finding is that MR1 differs very little across individuals – with few known genetic variants in the human population. "Thus, understanding immune activation mediated via MR1 may pave the way for therapeutic interventions with broad utility," Dr Illing said.
She added that next steps for investigation will confirm whether Vitamin B6 and related molecules are displayed by the MR1 of cancer cells at altered levels to healthy body cells, thus enabling specific cancer targeting, or if other small molecules displayed by MR1 may help differentiate cancerous and healthy cells.
