Multi-omics Characterization of Response to PD-1 Inhibitors in Advanced Melanoma
Trilla-Fuertes, Lucia (Hospital Universitario La Paz (Madrid))
Gámez-Pozo, Angelo (Biomedica Molecular Medicine SL)
Prado-Vázquez, Guillermo (Biomedica Molecular Medicine SL)
López-Vacas, Rocío (Hospital Universitario La Paz (Madrid))
Soriano, Virtudes (Grupo Español Multidisciplinar de Melanoma (GEM))
Garicano, Fernando (Hospital de Galdakao (Usansolo, Biscaia))
Lecumberri, M. José (Complejo Hospitalario de Navarra)
Rodríguez de la Borbolla, María (Hospital Universitario Virgen de Valme (Sevilla, Andalusia))
Majem Tarruella, Margarita (Institut d'Investigació Biomèdica Sant Pau)
Pérez-Ruiz, Elisabeth (Hospital Universitario Virgen de la Victoria (Màlaga, Andalusia))
González-Cao, María (Hospital Quirón Dexeus)
Oramas, Juana (Hospital Universitario de Canarias (La Laguna))
Magdaleno, Alejandra (Hospital Universitario de Elche y Vega Baja)
Fra, Joaquín (Hospital Universitario Río Hortega (Valladolid))
Martín Carnicero, Alfonso (Hospital San Pedro de Alcántara)
Corral, Mónica (Hospital Clínico Universitario "Lozano Blesa" de Zaragoza)
Puértolas, Teresa (Hospital Universitario Miguel Servet (Saragossa))
Ramos-Ruiz, Ricardo (Parque Científico de Madrid)
Dittmann, Antje (University/ETH Zurich)
Nanni, Paolo (University/ETH Zurich)
Fresno Vara, Juan Ángel (Instituto de Salud Carlos III)
Espinosa, Enrique (Hospital Universitario La Paz (Madrid))
Universitat Autònoma de Barcelona

Data:	2023
Resum:	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.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Immunotherapy response ; Inflammatory response ; Melanoma ; Multi-omics ; Protein processing in the endoplasmic reticulum
Publicat a:	Cancers, Vol. 15 Núm. 17 (september 2023) , p. 4407, ISSN 2072-6694

DOI: 10.3390/cancers15174407
PMID: 37686682

13 p, 1.5 MB

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Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut de Recerca Sant Pau
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