Multi-omics Characterization of Response to PD-1 Inhibitors in Advanced Melanoma.
Por:
Trilla-Fuertes L, Gámez-Pozo A, Prado-Vázquez G, López-Vacas R, Soriano V, Garicano F, Lecumberri MJ, Rodríguez de la Borbolla M, Majem M, Pérez-Ruiz E, González-Cao M, Oramas J, Magdaleno A, Fra J, Martín-Carnicero A, Corral M, Puértolas T, Ramos-Ruiz R, Dittmann A, Nanni P, Fresno Vara JÁ, Espinosa E
Publicada:
3 sep 2023
Ahead of Print:
3 sep 2023
Resumen:
Immunotherapy improves the survival of patients with advanced melanoma, 40% of whom become long-term responders. However, not all patients respond to immunotherapy. Further knowledge of the processes involved in the response and resistance to immunotherapy is still needed. In this study, clinical paraffin samples from fifty-two advanced melanoma patients treated with anti-PD-1 inhibitors were assessed via high-throughput proteomics and RNA-seq. The obtained proteomics and transcriptomics data were analyzed using multi-omics network analyses based on probabilistic graphical models to identify those biological processes involved in the response to immunotherapy. Additionally, proteins related to overall survival were studied. The activity of the node formed by the proteins involved in protein processing in the endoplasmic reticulum and antigen presentation machinery was higher in responders compared to non-responders; the activity of the immune and inflammatory response node was also higher in those with complete or partial responses. A predictor for overall survival based on two proteins (AMBP and PDSM5) was defined. In summary, the response to anti-PD-1 therapy in advanced melanoma is related to protein processing in the endoplasmic reticulum, and also to genes involved in the immune and inflammatory responses. Finally, a two-protein predictor can define survival in advanced disease. The molecular characterization of the mechanisms involved in the response and resistance to immunotherapy in melanoma leads the way to establishing therapeutic alternatives for patients who will not respond to this treatment.
Filiaciones:
Trilla-Fuertes L:
Molecular Oncology Laboratory, Hospital Universitario La Paz-IdiPAZ, 28046 Madrid, Spain
Gámez-Pozo A:
Molecular Oncology Laboratory, Hospital Universitario La Paz-IdiPAZ, 28046 Madrid, Spain
Biomedica Molecular Medicine SL, 28049 Madrid, Spain
Prado-Vázquez G:
Molecular Oncology Laboratory, Hospital Universitario La Paz-IdiPAZ, 28046 Madrid, Spain
Biomedica Molecular Medicine SL, 28049 Madrid, Spain
López-Vacas R:
Molecular Oncology Laboratory, Hospital Universitario La Paz-IdiPAZ, 28046 Madrid, Spain
Soriano V:
Instituto Valenciano de Oncología, 46009 Valencia, Spain
Spanish Melanoma Group (GEM), 08024 Barcelona, Spain
Garicano F:
Spanish Melanoma Group (GEM), 08024 Barcelona, Spain
Hospital de Galdakao, 48960 Galdakao, Spain
Lecumberri MJ:
Spanish Melanoma Group (GEM), 08024 Barcelona, Spain
Complejo Hospitalario de Navarra, 31008 Pamplona, Spain
Rodríguez de la Borbolla M:
Spanish Melanoma Group (GEM), 08024 Barcelona, Spain
Hospital de Valme, 41014 Sevilla, Spain
Majem M:
Spanish Melanoma Group (GEM), 08024 Barcelona, Spain
Hospital de la Santa Creu i Sant Pau, 08001 Barcelona, Spain
Pérez-Ruiz E:
Spanish Melanoma Group (GEM), 08024 Barcelona, Spain
Unidad de Gestión Clínica Intercentros (UGCI) de Oncología Médica, Hospitales Universitarios Regional y Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospitales Universitarios Regional y Virgen de la Victoria, 29010 Málaga, Spain
González-Cao M:
Spanish Melanoma Group (GEM), 08024 Barcelona, Spain
Hospital Quirón Dexeus, 08028 Barcelona, Spain
Oramas J:
Spanish Melanoma Group (GEM), 08024 Barcelona, Spain
Hospital Universitario de Canarias-San Cristóbal de la Laguna, 38320 Tenerife, Spain
Magdaleno A:
Spanish Melanoma Group (GEM), 08024 Barcelona, Spain
Hospital Universitario de Elche y Vega Baja, 03203 Alicante, Spain
Fra J:
Spanish Melanoma Group (GEM), 08024 Barcelona, Spain
Hospital Universitario Río Hortega, 47012 Valladolid, Spain
Martín-Carnicero A:
Spanish Melanoma Group (GEM), 08024 Barcelona, Spain
Hospital San Pedro, 27347 Logroño, Spain
Corral M:
Spanish Melanoma Group (GEM), 08024 Barcelona, Spain
Hospital Clínico Lozano Blesa, 50009 Zaragoza, Spain
Puértolas T:
Spanish Melanoma Group (GEM), 08024 Barcelona, Spain
Hospital Universitario Miguel Servet, 50009 Zaragoza, Spain
Ramos-Ruiz R:
Genomics Unit, Parque Científico de Madrid, 28049 Madrid, Spain
Dittmann A:
Functional Genomics Center Zurich, University/ETH Zurich, 8092 Zurich, Switzerland
Nanni P:
Functional Genomics Center Zurich, University/ETH Zurich, 8092 Zurich, Switzerland
Fresno Vara JÁ:
Molecular Oncology Laboratory, Hospital Universitario La Paz-IdiPAZ, 28046 Madrid, Spain
Biomedica Molecular Medicine SL, 28049 Madrid, Spain
CIBERONC, ISCIII, 28222 Madrid, Spain
Espinosa E:
Spanish Melanoma Group (GEM), 08024 Barcelona, Spain
CIBERONC, ISCIII, 28222 Madrid, Spain
Medical Oncology Service, Hospital Universitario La Paz, 28046 Madrid, Spain
Green Published, gold, All Open Access, Gold, Green
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