title: Defective generation and maturation of dendritic cells from monocytes in colorectal cancer patients during the course of disease.
abstract: Colorectal cancer (CRC) is the second-leading cause of cancer-related deaths in Western countries. Today, the role of the host's immune system in controlling the progression and spread of solid tumors is broadly established. Tumor immunosurveillance escape mechanisms, such as those involving dendritic cells (DCs), the most important antigen-presenting cells, are likewise recognized processes involved in cancer. The present study evaluates the ability of CRC patients to generate DCs in vitro from circulating monocytes at both pre- and post-operative timepoints; the results are correlated with the stage of disease to shed light on the systemic immune statuses of CRC patients. Our data showed that patients' DCs had lower co-stimulatory molecule expression and were less able to present antigens to allogeneic T cells compared to healthy controls' (HC) DCs. Furthermore altered cytokine secretion, such as increased IL-10 and reduced IL-12 and TNF-α, was observed. At the post-operative timepoints we observed a recovery of the patients' ability to generate immature DCs, compared to HCs, but the maturational capacity remained affected. Our study conclusively highlights the persistently impaired in vitro generation of fully mature and functional DCs, which appears to be more altered during advanced stages. This work sheds light on a dendritic cell-based tumor immune escape mechanism that could be useful for the development of more effective immunotherapeutic strategies.
authors.affiliation: Laboratory of Immunology, Department of Clinical and Experimental Medicine, University of Pisa, via Roma, 67, Pisa 56126, Italy. giulia.orsini@for.unipi.it.
authors.forename: Giulia
authors.initials: G
authors.lastname: Orsini
authors.forename: Annalisa
authors.initials: A
authors.lastname: Legitimo
authors.forename: Alessandra
authors.initials: A
authors.lastname: Failli
authors.forename: Paola
authors.initials: P
authors.lastname: Ferrari
authors.forename: Andrea
authors.initials: A
authors.lastname: Nicolini
authors.forename: Roberto
authors.initials: R
authors.lastname: Spisni
authors.forename: Paolo
authors.initials: P
authors.lastname: Miccoli
authors.forename: Rita
authors.initials: R
authors.lastname: Consolini
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000473:pathology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
chemical_list: D014409:Tumor Necrosis Factor-alpha