Frameshifting ID’d in Protein Synthesis by Ribosomes of Melanoma Cells Missing the Amino Acid Tryptophan; First Time Such Frameshifting Observed in Human Cells; Aberrant Proteins Produced As Result; Findings May Offer Therapeutic Insights

Cancers like melanoma are hard to treat, not least because they have a varied bag of tricks for defeating or evading treatments. A combined research effort by scientists at the Weizmann Institute of Science in Israel and researchers in the Netherlands Cancer Institute in Amsterdam and the University of Oslo, Norway, shows exactly how tumors, in their battles to survive, will go so far as to starve themselves in order to keep the immune cells that would eradicate them from functioning. The new work was published online on December 16 in Nature (https://www.nature.com/articles/s41586-020-03054-1). The article is titled “Anti-Tumour Immunity Induces Aberrant Peptide Presentation in Melanoma.” The immunotherapies currently administered for melanomas work by removing obstacles that keep immune cells called T-cells from identifying and killing tumor cells. Recent research suggested that in melanoma, another blocker could assist the T-cells, this one to stop an enzyme called IDO1 that is overproduced by the cancer cells. IDO1 breaks down an essential amino acid, tryptophan, which is needed to make proteins, in the process leaving behind tryptophan breakdown byproducts that suppress the immune response. But IDO1 blockers did not fare well in clinical trials, suggesting more knowledge was needed--including how the cancer cells, which also require tryptophan, can function after they have destroyed this resource. The research team, including the group of Professor Yardena Samuels (http://www.weizmann.ac.il/mcb/Samuels/) of Weizmann’s Molecular Cell Biology Department, members of the lab of Professor Reuven Agami (https://www.nki.nl/research/research-groups/reuven-agami/) of the Netherlands Cancer Institute; Dr.
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