A Call to Arms

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Team discovers key pathway that helps the immune system target diseased and cancerous cells.
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The mechanism identified in this study may enhance the body’s ability to target cancer cells and influence susceptibility to certain diseases.
You can run but you can’t hide. That is most often the case with diseased or cancerous cells that are present in our body. This is because the immune system—our body’s police force—has a special way of spotting and destroying these cells.
 
Every cell in the body displays short fragments of damaged or abnormal proteins (antigens)—captured from within or outside the cell—on a protein known as the major histocompatibility complex (MHC). 
 
Antigens that are captured inside the cell (eg, those that are made within a diseased cell) are presented on MHC class I molecules. Conversely, antigens that are captured from outside the cell (eg, those that are derived from bacteria or viruses) are presented on MHC class II molecules. 
 
A paradigm-shifting study led by PM Cancer Centre Senior Scientist Dr. Naoto Hirano has upended this classical understanding of antigen presentation in a paper that was published in the preeminent journal, Nature Communications.
 
Dr. Hirano and his team discovered a specific type of MHC class II molecule (HLA-DP84Gly) that can display antigens captured from both inside and outside of the cell. The team discovered that this was the result of a single change in the HLA-DP84Gly gene, which occurred fairly recently in our evolutionary development as it is only present in humans and chimpanzees.
 
“It’s possible that this genetic change had evolutionary advantages that enabled the immune system to spot and destroy diseased or cancerous cells more efficiently,” explains Dr. Hirano. “Further research will be needed to determine if this mechanism conferred a distinct health advantage in people that have this particular HLA gene.”
 
This work was supported by the National Institutes of Health, the Ontario Institute for Cancer Research, the Province of Ontario, the Japan Society for the Promotion of Science, a Knudson Postdoctoral Fellowship, a Guglietti Fellowship Award, a Frederick Banting and Charles Best Canada Graduate Scholarship and The Princess Margaret Cancer Foundation. TK holds a Tier 2 Canada Research Chair in Proteomics in Cancer Research.
 
Yamashita Y, Anczurowski M, Nakatsugawa M, Tanaka M, Kagoya Y, Sinha A, Chamoto K, Ochi T, Guo T, Saso K, Butler MO, Minden MD, Kislinger T, Hirano N. HLA-DP84Gly constitutively presents endogenous peptides generated by the class I antigen processing pathway. Nat Commun. 2017 May 10;8:15244. doi:10.1038/ncomms15244.