Promising New Target for Cancer Immunotherapy

Sensing infection and cellular change is essential for effective immunity. Human cells have a specialized chemical called MR1 on their surface. Although the range of metabolite sensing is unknown, MR1 permits the detection of specific small-molecule metabolites from microbial and cellular sources.

Researchers at the Monash University Biomedicine Discovery Institute have discovered a type of vitamin B6 coupled to MR1 that interacts with tumor-reactive immune cells. Their findings were published in PNAS. Researchers from the University of Melbourne co-led an international collaborative team that worked on the project.

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. 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.”

Dr. Patricia T. Illing, Department of Biochemistry and Molecular Biology, Monash University

The structural resolution of the interactions between MR1 and Vitamin B6, the objective mass spectrometry analysis of small molecules bound to MR1, and immunological assays conducted 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 were crucial to this investigation.

Although it is currently unclear whether the Vitamin B6 molecule can be used in therapeutics, “Understanding the breadth of MR1 mediated immunity has the capacity to illuminate routes for therapeutic intervention,” Dr. Illing said.

It is significant that MR1 varies relatively little between people and that there are not many known genetic variations in the human population.

Thus, understanding immune activation mediated via MR1 may pave the way for therapeutic interventions with broad utility.”

Dr. Patricia T. Illing, Department of Biochemistry and Molecular Biology, Monash University

She went on to say that further research will determine whether the MR1 of cancer cells exhibits Vitamin B6 and related molecules at different levels than those of healthy body cells, allowing for targeted cancer, or whether other small molecules displayed by MR1 may aid in the differentiation of cancerous and healthy cells.