title: Alcohol exposure differentially effects anti-tumor immunity in females by altering dendritic cell function.
abstract: Dendritic cells (DCs) are a critical component of anti-tumor immunity due to their ability to induce a robust immune response to antigen (Ag). Alcohol was previously shown to reduce DC ability to present foreign Ag and promote pro-inflammatory responses in situations of infection and trauma. However the impact of alcohol exposure on generation of an anti-tumor response, especially in the context of generation of an immune vaccine has not been examined. In the clinic, DC vaccines are typically generated from autologous blood, therefore prior exposure to substances such as alcohol may be a critical factor to consider regarding the effectiveness in generating an immune response. In this study, we demonstrate for the first time that ethanol differentially affects DC and tumor Ag-specific T cell responses depending on sex. Signaling pathways were found to be differentially regulated in DC in females compared to males and these differences were exacerbated by ethanol treatment. DC from female mice treated with ethanol were unable to activate Ag-specific cytotoxic T cells (CTL) as shown by reduced expression of CD44, CD69, and decreased production of granzyme B and IFNγ. Furthermore, although FOXO3, an immune suppressive mediator of DC function, was found to be upregulated in DC from female mice, ethanol related suppression was independent of FOXO3. These findings demonstrate for the first time differential impacts of alcohol on the immune system of females compared to males and may be a critical consideration for determining the effectiveness of an immune based therapy for cancer in patients that consume alcohol.
authors.affiliation: Loyola University Chicago, Department of Surgery, Cardinal Bernardin Cancer Center, Maywood, IL 60153, USA.
authors.forename: Matthew G
authors.initials: MG
authors.lastname: Thompson
authors.affiliation: Loyola University Chicago, Department of Surgery, Cardinal Bernardin Cancer Center, Maywood, IL 60153, USA.
authors.forename: Flor
authors.initials: F
authors.lastname: Navarro
authors.affiliation: Loyola University Chicago, Department of Surgery, Cardinal Bernardin Cancer Center, Maywood, IL 60153, USA.
authors.forename: Lennox
authors.initials: L
authors.lastname: Chitsike
authors.affiliation: Loyola University Chicago, Department of Surgery, Cardinal Bernardin Cancer Center, Maywood, IL 60153, USA.
authors.forename: Luis
authors.initials: L
authors.lastname: Ramirez
authors.affiliation: Loyola University Chicago, Department of Surgery, Cardinal Bernardin Cancer Center, Maywood, IL 60153, USA; University of Colorado Denver, Department of Surgery, Aurora, CO, USA.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Kovacs
authors.affiliation: Loyola University Chicago, Department of Surgery, Cardinal Bernardin Cancer Center, Maywood, IL 60153, USA. Electronic address: swatkins1@luc.edu.
authors.forename: Stephanie K
authors.initials: SK
authors.lastname: Watkins
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D000071316:Forkhead Box Protein O3 / Q000096:biosynthesis; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000276:immunology; D007111:Immunity, Cellular / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism; D012727:Sex Characteristics
chemical_list: D000071316:Forkhead Box Protein O3; C474033:FoxO3 protein, mouse; D000949:Histocompatibility Antigens Class II; D000431:Ethanol
keywords: Alcohol; Anti-tumor immunity; Cytotoxic T cell; Dendritic cell; Sex