OUH scientists demonstrate that translational mistakes can be promising targets of immunotherapy

From left: Laos, Olweus and Milek Nielsen. (photo: Cathrine Knetter Hoel)
From left: Laos, Olweus and Milek Nielsen. (photo: Cathrine Knetter Hoel)

Johanna Olweus, head of the "Experimental Immunotherapy Group" at the institute for Cancer Research, and scientists Dr. Morten Milek Nielsen and Dr. Maarja Laos in her group, have played a key role in an exciting collaborative project led by The Netherlands Cancer Institute. The collaboration has resulted in an groundbreaking paper recently published in Nature, entitled "Tryptophan depletion results in tryptophan-to-phenylalanine substitutants". The findings have received extra attention via a "News and Views" article in the same issue.

When cancer cells "starve", they can run out of specific building blocks for proteins (amino acids), in this case tryptophan. In the article in Nature, Agami and colleagues (NKI) demonstrate that the cancer cells instead can use alternative building blocks that are similar (phenylalanine), and that this causes the cancer cells to have altered proteins. They moreover show that fragments from these altered proteins appear on the outside of the cancer cells. The Olweus group then demonstrated that these altered protein fragments can be recognized by the immune system as foreign, in a similar way as fragments from viral proteins are recognized as foreign on virally infected cells. This opens up the possibility that such altered proteins can be used as targets for the immune cells in future immunotherapy.


The Nature article:
Tryptophan depletion results in tryptophan-to-phenylalanine substitutants.
Pataskar A, Champagne J, Nagel R, Kenski J, Laos M, Michaux J, Pak HS, Bleijerveld OB, Mordente K, Navarro JM, Blommaert N, Nielsen MM, Lovecchio D, Stone E, Georgiou G, de Gooijer MC, van Tellingen O, Altelaar M, Joosten RP, Perrakis A, Olweus J, Bassani-Sternberg M, Peeper DS, Agami R.
Nature. 2022 Mar 9. doi: 10.1038/s41586-022-04499-2. Online ahead of print.
PMID: 35264796

News and views article in the same Nature issue:
Immune cells alter genetic decoding in cancer.
Baranov PV, Atkins JF.
Nature. 2022 Mar 9. doi: 10.1038/d41586-022-00637-y. Online ahead of print.
PMID: 35264802

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