Pluto Bioinformatics

GSE142822: Anti-tumor immunity induces the presentation of aberrant peptides in melanoma

Bulk RNA sequencing

Extensive tumor inflammation, reflected by high levels of infiltrating T-cells and Interferon gamma (IFN) signaling, is thought to improve checkpoint immunotherapy response. However, many tumors escape by activating multiple cellular pathways that induce immunosuppression. One pivotal immune-suppressive mechanism is the production of Tryptophan metabolites along the kynurenine pathway by IFN-induced IDO1 enzyme production. However, phase III clinical trials using chemical inhibition of IDO1 in combination with PD1 pathway blockade failed to improve melanoma treatment, suggesting incomplete understanding of the role of IDO1 and the consequent Tryptophan degradation on mRNA translation and cancer progression. Here, we investigated the effects of prolonged IFN treatment on mRNA translation in melanoma cells by ribosome profiling. Our results suggest that IFN-induced IDO1-mediated Tryptophan depletion may play a key role in the immune recognition of melanoma cells, by inducing the production and presentation of aberrant peptides. SOURCE: Pierre-Rene Körner Netherlands Cancer Institute (NKI)

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