Sorting Transcriptomics Immune Information from Tumor Molecular Features Allows Prediction of Response to Anti-PD1 Therapy in Patients with Advanced Melanoma


Por: Trilla-Fuertes L., Gámez-Pozo A., Prado-Vázquez G., López-Vacas R., Zapater-Moros A., López-Camacho E., Lumbreras-Herrera M.I., Soriano V., Garicano F., Lecumberri M.J., de la Borbolla, MR, Majem M., Pérez-Ruiz E., González-Cao M., Oramas J., Magdaleno A., Fra J., Martín-Carnicero A., Corral M., Puértolas T., Ramos R., Vara, JAF, Espinosa E.

Publicada: 2 ene 2023 Ahead of Print: 2 ene 2023
Resumen:
Immunotherapy based on anti-PD1 antibodies has improved the outcome of advanced melanoma. However, prediction of response to immunotherapy remains an unmet need in the field. Tumor PD-L1 expression, mutational burden, gene profiles and microbiome profiles have been proposed as potential markers but are not used in clinical practice. Probabilistic graphical models and classificatory algorithms were used to classify melanoma tumor samples from a TCGA cohort. A cohort of patients with advanced melanoma treated with PD-1 inhibitors was also analyzed. We established that gene expression data can be grouped in two different layers of information: immune and molecular. In the TCGA, the molecular classification provided information on processes such as epidermis development and keratinization, melanogenesis, and extracellular space and membrane. The immune layer classification was able to distinguish between responders and non-responders to immunotherapy in an independent series of patients with advanced melanoma treated with PD-1 inhibitors. We established that the immune information is independent than molecular features of the tumors in melanoma TCGA cohort, and an immune classification of these tumors was established. This immune classification was capable to determine what patients are going to respond to immunotherapy in a new cohort of patients with advanced melanoma treated with PD-1 inhibitors Therefore, this immune signature could be useful to the clinicians to identify those patients who will respond to immunotherapy.

Filiaciones:
Trilla-Fuertes L.:
 Hosp Univ La Paz IdiPAZ, Mol Oncol Lab, Madrid 28046, Spain

Gámez-Pozo A.:
 Hosp Univ La Paz IdiPAZ, Mol Oncol Lab, Madrid 28046, Spain

 Biomed Mol Med SL, Madrid 28049, Spain

Prado-Vázquez G.:
 Hosp Univ La Paz IdiPAZ, Mol Oncol Lab, Madrid 28046, Spain

 Biomed Mol Med SL, Madrid 28049, Spain

López-Vacas R.:
 Hosp Univ La Paz IdiPAZ, Mol Oncol Lab, Madrid 28046, Spain

Zapater-Moros A.:
 Hosp Univ La Paz IdiPAZ, Mol Oncol Lab, Madrid 28046, Spain

 Biomed Mol Med SL, Madrid 28049, Spain

López-Camacho E.:
 Biomed Mol Med SL, Madrid 28049, Spain

Lumbreras-Herrera M.I.:
 Hosp Univ La Paz IdiPAZ, Mol Oncol Lab, Madrid 28046, Spain

Soriano V.:
 Inst Valenciano Oncol, Valencia 46009, Spain

 Spanish Melanoma Grp GEM, Barcelona 08024, Spain

Garicano F.:
 Spanish Melanoma Grp GEM, Barcelona 08024, Spain

 Hosp Galdakao, Bizkaia 48960, Spain

Lecumberri M.J.:
 Spanish Melanoma Grp GEM, Barcelona 08024, Spain

 Complejo Hosp Navarra, Pamplona 31008, Spain

de la Borbolla, MR:
 Spanish Melanoma Grp GEM, Barcelona 08024, Spain

 Hosp Valme, Seville 41014, Spain

Majem M.:
 Spanish Melanoma Grp GEM, Barcelona 08024, Spain

 Hosp Santa Creu & Sant Pau, Barcelona 08025, Spain

Pérez-Ruiz E.:
 Spanish Melanoma Grp GEM, Barcelona 08024, Spain

 Hosp Costa Sol, Marbella 29603, Spain

González-Cao M.:
 Spanish Melanoma Grp GEM, Barcelona 08024, Spain

 Hosp Quiron Dexeus, Barcelona 08028, Spain

Oramas J.:
 Spanish Melanoma Grp GEM, Barcelona 08024, Spain

 Hosp Univ Canarias San Cristobal Laguna, San Cristobal la Laguna 38320, Spain

Magdaleno A.:
 Spanish Melanoma Grp GEM, Barcelona 08024, Spain

 Hosp Univ Elche & Vega Baja, Elche 03203, Spain

Fra J.:
 Spanish Melanoma Grp GEM, Barcelona 08024, Spain

 Hosp Univ Rio Hortega, Valladolid 47012, Spain

Martín-Carnicero A.:
 Spanish Melanoma Grp GEM, Barcelona 08024, Spain

 Hosp San Pedro, Logrono 26006, Spain

Corral M.:
 Spanish Melanoma Grp GEM, Barcelona 08024, Spain

 Hosp Clin Lozano Blesa, Zaragoza 50009, Spain

Puértolas T.:
 Spanish Melanoma Grp GEM, Barcelona 08024, Spain

 Hosp Univ Miguel Servet, Zaragoza 50009, Spain

Ramos R.:
 Genom Unit, Parque Cientif Madrid, Madrid 28049, Spain

Vara, JAF:
 Hosp Univ La Paz IdiPAZ, Mol Oncol Lab, Madrid 28046, Spain

 Biomed Mol Med SL, Madrid 28049, Spain

 ISCIII, CIBERONC, Madrid 28029, Spain

Espinosa E.:
 Spanish Melanoma Grp GEM, Barcelona 08024, Spain

 ISCIII, CIBERONC, Madrid 28029, Spain

 Hosp Univ La Paz, Med Oncol Serv, Madrid 28046, Spain
ISSN: 16616596
Editorial
MDPI, ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND, Suiza
Tipo de documento: Article
Volumen: 24 Número: 1
Páginas:
WOS Id: 000909446200001
ID de PubMed: 36614248
imagen gold, Green Published, All Open Access, Gold, Green

MÉTRICAS