title: IL-17/IL-10 double-producing T cells: new link between infections, immunosuppression and acute myeloid leukemia.
abstract: BACKGROUND
  Acute myeloid leukemia (AML) is an incurable disease with fatal infections or relapse being the main causes of death in most cases. In particular, the severe infections occurring in these patients before or during any treatment suggest an intrinsic alteration of the immune system. In this respect, IL-17-producing T helper (Th17) besides playing a key role in regulating inflammatory response, tumor growth and autoimmune diseases, have been shown to protect against bacterial and fungal pathogens. However, the role of Th17 cells in AML has not yet been clarified.
  
  
  METHODS
  T cell frequencies were assessed by flow cytometry in the peripheral blood of 30 newly diagnosed AML patients and 30 age-matched healthy volunteers. Cytokine production was determined before and after culture of T cells with either Candida Albicans or AML blasts. Statistical analyses were carried out using the paired and unpaired two-tailed Student's t tests and confirmed with the non parametric Wilcoxon signed-rank test.
  
  
  RESULTS
  A strong increase of Th17 cells producing immunosuppressive IL-10 was observed in AML patients compared with healthy donors. In addition, stimulation of AML-derived T cells with a Candida albicans antigen induced significantly lower IFN-γ production than that observed in healthy donors; intriguingly, depletion of patient Th17 cells restored IFN-γ production after stimulation. To address the role of AML blasts in inducing Th17 alterations, CD4+ cells from healthy donors were co-cultured with CD33+ blasts: data obtained showed that AML blasts induce in healthy donors levels of IL-10-producing Th17 cells similar to those observed in patients.
  
  
  CONCLUSIONS
  In AML patients altered Th17 cells actively cause an immunosuppressive state that may promote infections and probably tumor escape. Th17 cells could thus represent a new target to improve AML immunotherapy.
authors.affiliation: Hematology Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. gerardo.musuraca@irst.emr.it.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Musuraca
authors.affiliation: Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. serena.dematteis@irst.emr.it.
authors.forename: Serena
authors.initials: S
authors.lastname: De Matteis
authors.affiliation: Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. roberta.napolitano@irst.emr.it.
authors.forename: Roberta
authors.initials: R
authors.lastname: Napolitano
authors.affiliation: Department of Hematology and Oncological Sciences 'L. and A. Seràgnoli', University of Bologna, Bologna, Italy. cristina.papayannidis@unibo.it.
authors.forename: Cristina
authors.initials: C
authors.lastname: Papayannidis
authors.affiliation: Department of Hematology and Oncological Sciences 'L. and A. Seràgnoli', University of Bologna, Bologna, Italy. viviana.guadagnuolo2@unibo.it.
authors.forename: Viviana
authors.initials: V
authors.lastname: Guadagnuolo
authors.affiliation: Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. francesco.fabbri@irst.emr.it.
authors.forename: Francesco
authors.initials: F
authors.lastname: Fabbri
authors.affiliation: Hematology Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. delia.cangini@irst.emr.it.
authors.forename: Delia
authors.initials: D
authors.lastname: Cangini
authors.affiliation: Hematology Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. michela.ceccolini@irst.emr.it.
authors.forename: Michela
authors.initials: M
authors.lastname: Ceccolini
authors.affiliation: Hematology Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. maria.giannini@irst.emr.it.
authors.forename: Maria Benedetta
authors.initials: MB
authors.lastname: Giannini
authors.affiliation: Hematology Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. alessandro.lucchesi@irst.emr.it.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Lucchesi
authors.affiliation: Hematology Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. sonia.ronconi@irst.emr.it.
authors.forename: Sonia
authors.initials: S
authors.lastname: Ronconi
authors.affiliation: Department of Hematology and Oncological Sciences 'L. and A. Seràgnoli', University of Bologna, Bologna, Italy. paolo.mariotti5@unibo.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Mariotti
authors.affiliation: Internal Medicine Unit, Infermi Hospital, Faenza, Italy. p.savini@ausl.ra.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Savini
authors.affiliation: Haematology Unit, Santa Maria delle Croci Hospital, Ravenna, Italy. monica.tani@ausl.ra.it.
authors.forename: Monica
authors.initials: M
authors.lastname: Tani
authors.affiliation: Hematology Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. pierpaolo.fattori@irst.emr.it.
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: Fattori
authors.affiliation: Immunotherapy Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. massimo.guidoboni@irst.emr.it.
authors.forename: Massimo
authors.initials: M
authors.lastname: Guidoboni
authors.affiliation: Department of Hematology and Oncological Sciences 'L. and A. Seràgnoli', University of Bologna, Bologna, Italy. giovanni.martinelli2@unibo.it.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Martinelli
authors.affiliation: Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. wainer.zoli@irst.emr.it.
authors.forename: Wainer
authors.initials: W
authors.lastname: Zoli
authors.affiliation: Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. dino.amadori@irst.emr.it.
authors.forename: Dino
authors.initials: D
authors.lastname: Amadori
authors.affiliation: Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. silvia.carloni@irst.emr.it.
authors.forename: Silvia
authors.initials: S
authors.lastname: Carloni
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001752:Blast Crisis / Q000276:immunology; D002176:Candida albicans / Q000276:immunology; D002177:Candidiasis / Q000150:complications / Q000276:immunology* / Q000382:microbiology; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007165:Immunosuppression Therapy; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis*; D020381:Interleukin-17 / Q000096:biosynthesis*; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000150:complications / Q000276:immunology* / Q000382:microbiology*; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D063268:Sialic Acid Binding Ig-like Lectin 3 / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology
chemical_list: D016207:Cytokines; D020381:Interleukin-17; D063268:Sialic Acid Binding Ig-like Lectin 3; D016753:Interleukin-10; D007371:Interferon-gamma