Marina Tusup1,2, Phil F Cheng1,2, Ernesto Picardi3,4, Austeja Raziunaite1,2, Reinhard Dummer1,2, Mitchell P Levesque1,2, Lars E French1,2,5, Emmanuella Guenova1,2,6, Thomas M Kundig1,2, Steve Pascolo1,2. 1. Department of Dermatology, University Hospital of Zürich, Gloriastrasse 31, 8091 Zürich, Switzerland. 2. Faculty of Medicine, University of Zürich, 8091 Zürich, Switzerland. 3. Department of Biosciences, Biotechnology and Biopharmaceutics, University of Bari "A. Moro", 70121 Bari, Italy. 4. Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies (IBIOM), National Research Council, 70126 Bari, Italy. 5. Department of Dermatology and Allergy, University Hospital, LMU Munich, 80336 Munich, Germany. 6. Department of Dermatology, Lausanne University Hospital and Faculty of Biology and Medicine, University of Lausanne, 1015 Lausanne, Switzerland.
Abstract
BACKGROUND: RNA editing is a highly conserved posttranscriptional mechanism that contributes to transcriptome diversity. In mammals, it includes nucleobase deaminations that convert cytidine (C) into uridine (U) and adenosine (A) into inosine (I). Evidence from cancer studies indicates that RNA-editing enzymes promote certain mechanisms of tumorigenesis. On the other hand, recoding editing in mRNA can generate mutations in proteins that can participate in the Major Histocompatibility Complex (MHC) ligandome and can therefore be recognized by the adaptive immune system. Anti-cancer treatment based on the administration of immune checkpoint inhibitors enhance these natural anti-cancer immune responses. RESULTS: Based on RNA-Seq datasets, we evaluated the editome of melanoma cell lines generated from patients pre- and post-immunotherapy with immune checkpoint inhibitors. Our results reveal a differential editing in Arthrobacter luteus (Alu) sequences between samples pre-therapy and relapses during therapy with immune checkpoint inhibitors. CONCLUSION: These data pave the way towards the development of new diagnostics and therapies targeted to editing that could help in preventing relapses during immunotherapies.
BACKGROUND: RNA editing is a highly conserved posttranscriptional mechanism that contributes to transcriptome diversity. In mammals, it includes nucleobase deaminations that convert cytidine (C) into uridine (U) and adenosine (A) into inosine (I). Evidence from cancer studies indicates that RNA-editing enzymes promote certain mechanisms of tumorigenesis. On the other hand, recoding editing in mRNA can generate mutations in proteins that can participate in the Major Histocompatibility Complex (MHC) ligandome and can therefore be recognized by the adaptive immune system. Anti-cancer treatment based on the administration of immune checkpoint inhibitors enhance these natural anti-cancer immune responses. RESULTS: Based on RNA-Seq datasets, we evaluated the editome of melanoma cell lines generated from patients pre- and post-immunotherapy with immune checkpoint inhibitors. Our results reveal a differential editing in Arthrobacter luteus (Alu) sequences between samples pre-therapy and relapses during therapy with immune checkpoint inhibitors. CONCLUSION: These data pave the way towards the development of new diagnostics and therapies targeted to editing that could help in preventing relapses during immunotherapies.
Entities:
Keywords:
ADAR; Alu sequences; editing; immune checkpoint inhibitors; immunotherapy; melanoma
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