title: Dynamics of T-cell infiltration during the course of ovarian cancer: the gradual shift from a Th17 effector cell response to a predominant infiltration by regulatory T-cells.
abstract: The type of immune cells that are present within the tumor microenvironment can play a crucial role in the survival of patients. However, little is known about the dynamics of the tumor-infiltrating immune cells during disease progression. We studied the immune cells that infiltrated the tumor tissues of ovarian cancer patients at different stages of disease. The early stages of development of ovarian carcinomas were characterized by a strong Th17 immune response, whereas in stage II patients, recruitment of high numbers of Th1 cells was observed. In disseminated tumors (Stages III-IV), we detected a dominant population of Helios(+)  activated regulatory T cells (Tregs) along with high numbers of monocytes/macrophages and myeloid dendritic cells (mDCs). Tumor-infiltrating Tregs had markedly lower expression of CCR4 than circulating Tregs, and the numbers of tumor-infiltrating Tregs significantly correlated with the levels of CCL22 in ovarian tumor cell culture supernatants, suggesting their recruitment via a CCR4/CCL22 interaction. CCL22 was mainly produced by tumor cells, monocytes/macrophages and mDCs in the primary ovarian tumors, and its expression markedly increased in response to IFNγ. Taken together, the specific recruitment of Tregs, probably triggered by inflammatory stimuli, leads to a significant immune suppression in the advanced stages of ovarian cancer.
authors.affiliation: Department of Immunology, UK and University Hospital Motol, Prague, Czech Republic. anna.fialova@lfmotol.cuni.cz
authors.forename: Anna
authors.initials: A
authors.lastname: Fialová
authors.forename: Simona
authors.initials: S
authors.lastname: Partlová
authors.forename: Luděk
authors.initials: L
authors.lastname: Sojka
authors.forename: Hana
authors.initials: H
authors.lastname: Hromádková
authors.forename: Tomáš
authors.initials: T
authors.lastname: Brtnický
authors.forename: Jitka
authors.initials: J
authors.lastname: Fučíková
authors.forename: Petr
authors.initials: P
authors.lastname: Kocián
authors.forename: Lukáš
authors.initials: L
authors.lastname: Rob
authors.forename: Jiřina
authors.initials: J
authors.lastname: Bartůňková
authors.forename: Radek
authors.initials: R
authors.lastname: Spíšek
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D048708:Cell Growth Processes / Q000276:immunology; D045744:Cell Line, Tumor; D054422:Chemokine CCL22 / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D054398:Receptors, CCR4 / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism; D059016:Tumor Microenvironment / Q000276:immunology
chemical_list: C515482:CCL22 protein, human; C515354:CCR4 protein, human; D054422:Chemokine CCL22; D054398:Receptors, CCR4; D007371:Interferon-gamma