Immunosuppression by monocytic myeloid-derived suppressor cells in patients with pancreatic ductal carcinoma is orchestrated by STAT3

著者: Rosalinda Trovato, Alessandra Fiore, S Sartori, Stefania Canè, Rosalba Giugno, Luciano Cascione, Salvatore Paiella, Roberto Salvia, Francesco De Sanctis, Ornella Poffe, Cristina Anselmi, Francesca Hofer, Silvia Sartoris, Geny Piro, Carmine Carbone, Vincenzo Corbo, Rita T. Lawlor, Samantha Solito, Laura Pinton, Susanna Mandruzzato, Claudio Bassi, Aldo Scarpa, Vincenzo Bronte, Stefano Ugel - Journal for ImmunoTherapy of Cancer 2019 被引用: 187

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a highly devastating disease with an overall 5-year survival rate of less than 8%. New evidence indicates that PDAC cells release pro-inflammatory metabolites that induce a marked alteration of normal hematopoiesis, favoring the expansion and accumulation of myeloid-derived suppressor cells (MDSCs). We report here that PDAC patients show increased levels of both circulating and tumor-infiltrating MDSC-like cells. METHODS: The frequency of MDSC subsets in the peripheral blood was determined by flow cytometry in three independent cohorts of PDAC patients (total analyzed patients, n = 117). Frequency of circulating MDSCs was correlated with overall survival of PDAC patients. We also analyzed the frequency of tumor-infiltrating MDSC and the immune landscape in fresh biopsies. Purified myeloid cell subsets were tested in vitro for their T-cell suppressive capacity. RESULTS: cells. CONCLUSION: MDSC analysis aids in defining the immune landscape of PDAC patients for a more appropriate diagnosis, stratification and treatment.