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Francesca Rapino - GIGA ULiège : Impact of codon-biased translational regulation in melanoma immuneresponse


2019 - In the past years the discovery that our immune system is able to recognize and kill tumor cells led to effective treatments for many cancers. Among those melanoma, the deadliest form of skin cancer, has shown an impressive regression when treated with immunotherapy. Unfortunately, not all patients respond to the current immune treatments and some of them acquire resistance towards the drugs after some time. For these reasons, a better understanding of the events occurring in tumors when they face the immune system would be beneficial to improve melanoma patients’ prognosis. Protein synthesis occurs in cells by associating the codons of the mRNA to the specific aminoacid in the protein. This happens in the ribosomes by correctly pairing the mRNA codons to the tRNA anticodon: to this end tRNAs can be modified in order to increase the efficiency and the fidelity of the recognition of specific codons. We recently discovered that a specific tRNA modification (U34-mcm5s2) is needed for melanoma cells to become resistant to target therapy. In this project we want to understand if the U34-mcm5s2 modification plays a role in modulating melanoma response to the immune system. Also, we aim to understand if other tRNA modifications, or actors of translation fidelity, will be important to define melanoma immune response. This study will highlight new regulatory pathways and putative important targets for immunotherapy possibly ameliorating patient life.

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