Gética 2020

[ F I T C á n c e r - 6 ] 41 CO03. Total RNA-transcriptomics for identification of predictors of overall survival in metastatic melanoma patients treated with anti-PD-1 Barragán, Isabel 1,2 ; Laborda-Illanes, Aurora 2 ; Onieva, Juan Luis 2 ; Piñeiro, Pilar 2 ; Garrido-Aranda, Alicia 3 ; Xiao, Qingyang 1 ; Gallego, Elena 4 ; Robles-Podadera, Cynthia 3 ; Chica-Parrado, María Rosario 3 ; Prieto, Daniel 4 ; Sánchez, Alfonso 3 ; de Luque, Vanessa 3 ; Lozano, María José 5 ; Álvarez, Martina 3,5 ; Jiménez, Pedro 2 ; Alba, Emilio 3 ; Berciano-Gerrero, Miguel 2 ; Óliver, Javier 2 ; Cobo, Manuel 2 1 Section of Immuno-Oncology. Medical Oncology Service. Hospital Universitario Virgen de la Victoria. Biomedical Research Institute of Malaga (IBIMA). Málaga, España. 2 Pharmacoepigenetics Group. Department of Physiology and Pharmacology. Karolinska Institutet. Estocol- mo, Suecia. 3 Medical Oncology Service. Hospitales Universitario Virgen de la Victoria. Institute of Biomedical Research in Malaga (IBIMA). CIMES. Universidad de Málaga. Málaga, España. 4 Pathology Service. Hospital Universitario Virgen de la Victoria. Málaga, España. 5 Pathology Department. Universidad de Málaga. Málaga, España Background: Immune Checkpoint Blockade (ICB) achieves up to 45% of response in advanced non-small-cell lung cancer and melanoma. How- ever, its use is suboptimal because the resistance mechanisms are not defined and we lack good predictive biomarkers. This study aims at identify- ing functional biomarkers of response to anti-PD-1 treatment. Methods: A retrospective pilot cohort of 16 patients with metastatic cutaneous melanoma treated with Nivolumab was categorized into ex- treme good or bad responders according to best response and treatment duration. Total RNA from FFPE tumor tissues was subjected to transcrip- tomics profiling by RNA-seq with ribosomal RNA depletion. Differential expression was calculated with DeSeq2, and pathway analysis with GSEA. Survival analysis was performed using Kaplan-Mei- er method. Results: We have identified 140 genes as differ- entially expressed (DE) (adj p < 0.05) in good re- sponders to Nivolumab. Interestingly, the genes are in their majority expressed in immune cells, in particular in the B cell lineage. GSEA shows mainly processes related to immune response, with a high B cells involvement. In addition, 22 genes are asso- ciated with improved overall survival, among which there are several genes coding for specific regions of both variable and constant domains of immuno- globulin chains, and the tumor gene LGR5 , which is a cancer stem cells marker and is correlated with chemotherapy resistance in gastric cancer. Conclusion: This is the first study reporting a to- tal-ARNprofiling of patients treatedwith ICB. It reveals a comprehensive signature of immune-cells specific genes that delineate the response. The overrepresen- tation of B cell lineage genes suggests unprecedented hypotheses for the response mechanisms. COMUNICACIONES ORALES