Ariane Busso-Lopes (Campinas / BR), Daniella de Figueiredo (Campinas / BR), Tatiane De Rossi (Campinas / BR), Ana Karina de Oliveira (Campinas / BR), Nayane Galdino (São Paulo / BR), Rodrigo Cruz (Campinas / BR), Larissa Carvalho-Silva (Campinas / BR), Jamile Sá (Campinas / BR), Sami Yokoo (Campinas / BR), Reynaldo Magalhaes Melo (Campinas / BR), Jackson Gabriel Miyamoto (Campinas / BR), Maurício Camacho (Campinas / BR), Bianca Alves Pauletti (Campinas / BR), Romênia Domingues (Campinas / BR), Daniela Campos Granato (Campinas / BR), Elaine C Cardoso (Campinas / BR), Heloísa MA Prado (Campinas / BR), Wagner FO da Silva (Campinas / BR), Fabio Patroni (Campinas / BR), Gabriela Raposo (Rio de Janeiro / BR), Mariana Boroni (Rio de Janeiro / BR), Mariela Piccin (São Paulo / BR), Tiago Medina (São Paulo / BR), Guilherme Tamarindo (Campinas / BR), Sandra Dias (Campinas / BR), João Ormonde (Campinas / BR), Marcos Alborghetti (Campinas / BR), Mauricio Sforca (Campinas / BR), Ana Carolina Prado Ribeiro (São Paulo / DE), Thais Brandão (São Paulo / DE), Mariane Amano (São Paulo / BR), Miyuki Uno (São Paulo / DE), Alan Santos-Silva (Piracicaba / BR), Marcio Lopes (Piracicaba / BR), Kenneth Gollob (São Paulo / BR), Luiz Paulo Kowalski (São Paulo / BR), Adriana Franco Paes Leme (Campinas / BR)
Head and neck cancer (HNC) is ranked the seventh leading cause of cancer worldwide, with a 5-year survival rate of less than 50% in advanced cases. Together with tobacco smoking, alcohol drinking is one of the major risk factors for HNC. Despite the advances in understanding HNC progression, the mechanism involved in HNC initiation is largely unknown. Through spatially resolved and bulk proteomics using holistic and reductionist approaches, we demonstrate in a 94 patient-cohort that alcohol modifies the proteome pattern of stromal and epithelial cells, circulating immune cells, primary fibroblasts and their extracellular vesicles (EVs). Besides tissue biopsy-derived EVs, alcohol-treated fibroblasts and their EVs shape the immune response. In addition, a selected protein, identified in both biopsy-derived EVs and those from alcohol-treated fibroblasts, modulates the phenotype of specific immune cells. These results improve our understanding of the molecular changes induced by alcohol in multiple microenvironments, and highlight the role of EVs in expanding its toxicity.