Abstract 5416: RNA-seq and proteomics to identify response to immunotherapy in advanced melanoma: a Spanish Melanoma Group Study

Abstract Background: Prediction of response to immunotherapy remains an unmet need in the field of advanced melanoma. Methods: Computational analyses, including probabilistic graphical models, sparse k-means, and consensus cluster, were used to characterize melanoma TCGA samples. The implication of the identified processes in response to immunotherapy was then studied in an independent cohort of 53 patients with advanced melanoma and treated with PD-1 inhibitors. Paraffin samples from this cohort were analyzed using RNA-seq and mass-spectrometry proteomics. Results: In the TCGA cohort, there were two different layers of information: one related to molecular features of the tumor (based on keratinization, melanogenesis, and extracellular space), and one related to immune status. Therefore, two independent classifications of TCGA melanoma samples were established: molecular and immune. The immune classification distinguished between responders and not responders to immunotherapy in the second cohort (p= 0.0006, HR=6.52). Finally, high-throughput proteomics was used to characterize molecular mechanisms involved in response to immunotherapy, identifying several biological processes and proteins that may be relevant in treatment selection for patients who do not respond. Conclusions: We established that the immune information was independent of tumor molecular features in melanomas included in the TCGA. An immune classification of these tumors was established. This immune classification predicted response to immunotherapy in a new cohort of patients with advanced melanoma treated with PD-1 inhibitors. Finally, proteomics was used to identify possible targets in those patients who did not respond to immunotherapy. Citation Format: Lucia Trilla-Fuertes, Guillermo Prado-Vazquez, Angelo Gámez-Pozo, Rocio Lopez-Vacas, Maria Isabel Lumbreras Herrera, Virtudes Soriano, Fernando Garicano, Maria Jose Lecumberri, Maria Rodriguez, Margarita Majem, Elisabeth Perez, Maria Gonzalez-Cao, Juana Oramas, Alejandra Magdaleno, Joaquin Fra, Alfonso Martin, Monica Corral, Teresa Puertolas, Juan Angel Fresno Vara, Enrique Espinosa. RNA-seq and proteomics to identify response to immunotherapy in advanced melanoma: a Spanish Melanoma Group Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5416.