title: FOXO3, estrogen receptor alpha, and androgen receptor impact tumor growth rate and infiltration of dendritic cell subsets differentially between male and female mice.
abstract: Tumors evade immune recognition and destruction in many ways including the creation of an immune-suppressive tumor microenvironment (TME). Dendritic cells (DC) that infiltrate the TME are tolerogenic, and suppress effector T cells and anti-tumor activity. Previous reports demonstrated that a key regulator of tolerance in DC is the transcription factor FOXO3. Gender disparity has been studied in cancer in relation to incidence, aggressiveness, and prognosis. Few studies have touched on the importance in relation to impact on the immune system. In the current study, we show that there are significant differences in tumor growth between males and females. Additionally, frequencies and the function of FOXO3 expressed by DC subsets that infiltrate tumors vary between genders. Our results show for the first time that DC FOXO3 expression and function is altered in females. In vitro results indicate that these differences may be the result of exposure to estrogen. These differences may be critical considerations for the enhancement of immunotherapy for cancer.
authors.affiliation: Department of Surgery, Cardinal Bernardin Cancer Center, Loyola University Chicago, 2160 S. 1st Ave. Building 112, Maywood, IL, 60153, USA.
authors.forename: Matthew G
authors.initials: MG
authors.lastname: Thompson
authors.affiliation: Department of Surgery, Cardinal Bernardin Cancer Center, Loyola University Chicago, 2160 S. 1st Ave. Building 112, Maywood, IL, 60153, USA.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Peiffer
authors.affiliation: Department of Surgery, Cardinal Bernardin Cancer Center, Loyola University Chicago, 2160 S. 1st Ave. Building 112, Maywood, IL, 60153, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Larson
authors.affiliation: Department of Surgery, Cardinal Bernardin Cancer Center, Loyola University Chicago, 2160 S. 1st Ave. Building 112, Maywood, IL, 60153, USA.
authors.forename: Flor
authors.initials: F
authors.lastname: Navarro
authors.affiliation: Department of Surgery, Cardinal Bernardin Cancer Center, Loyola University Chicago, 2160 S. 1st Ave. Building 112, Maywood, IL, 60153, USA. swatkins1@luc.edu.
authors.forename: Stephanie K
authors.initials: SK
authors.lastname: Watkins
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000276:immunology*; D047628:Estrogen Receptor alpha / Q000276:immunology*; D005260:Female; D000071316:Forkhead Box Protein O3 / Q000235:genetics / Q000378:metabolism*; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008297:Male; D008546:Melanoma, Experimental / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011944:Receptors, Androgen / Q000276:immunology*; D012737:Sex Factors
chemical_list: D047628:Estrogen Receptor alpha; D000071316:Forkhead Box Protein O3; C474033:FoxO3 protein, mouse; D011944:Receptors, Androgen
keywords: Dendritic cells; Gender; Hormone receptors; Immunity; T cells; Tumor