Introduction of checkpoint inhibitors resulted in durable responses and improvements in overall survival in advanced RCC patients, but the treatment efficacy is widely variable, and a considerable number of patients are resistant to PD-1/PD-L1 inhibition. This variability of clinical response makes necessary the discovery of predictive biomarkers for patient selection. Previous findings showed that the epigenetic modifications, including an extensive microRNA-mediated regulation of tumor suppressor genes, are key features of RCC. Based on this biological background, we hypothesized that a miRNA expression profile directly identified in the peripheral lymphocytes of the patients before and after the nivolumab administration could represent a step toward a real-time monitoring of the dynamic changes during cancer evolution and treatment. Interestingly, we found a specific subset of miRNAs, called "lymphocyte miRNA signature", specifically induced in long-responder patients (CR, PR, or SD to nivolumab >18 months). Focusing on the clinical translational potential of miRNAs in controlling the expression of immune checkpoints, we identified the association between the plasma levels of soluble PD-1/PD-L1 and expression of some lymphocyte miRNAs. These findings could help the development of novel dynamic predictive biomarkers urgently needed to predict the potential response to immunotherapy and to guide clinical decision-making in RCC patients.
Cancers. 2020 Nov 16*** epublish ***
Lorena Incorvaia, Daniele Fanale, Giuseppe Badalamenti, Chiara Brando, Marco Bono, Ida De Luca, Laura Algeri, Annalisa Bonasera, Lidia Rita Corsini, Salvatore Scurria, Juan Lucio Iovanna, Antonio Russo, Viviana Bazan
Department of Biomedicine, Neuroscience and Advanced Diagnostics (Bi.N.D.), Section of Medical Oncology, University of Palermo, 90127 Palermo, Italy., Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, 90127 Palermo, Italy., Department of Surgical, Oncological and Oral Sciences, Section of Urology, University of Palermo, 90127 Palermo, Italy., Team Pancreatic Cancer, Centre de Recherche en Cancérologie de Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille Université and Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy, 13288 Marseille, France.