IL-17/IL-10 double-producing T cells: new link between infections, immunosuppression and acute myeloid leukemia

• Published in: Journal of translational medicine Vol. 13; no. 1; p. 229
• Main Authors: Musuraca, Gerardo, De Matteis, Serena, Napolitano, Roberta, Papayannidis, Cristina, Guadagnuolo, Viviana, Fabbri, Francesco, Cangini, Delia, Ceccolini, Michela, Giannini, Maria Benedetta, Lucchesi, Alessandro, Ronconi, Sonia, Mariotti, Paolo, Savini, Paolo, Tani, Monica, Fattori, Pier Paolo, Guidoboni, Massimo, Martinelli, Giovanni, Zoli, Wainer, Amadori, Dino, Carloni, Silvia
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 15-07-2015; BioMed Central
• Subjects: Adult; Aged; Aged, 80 and over; Analysis; Antigens; Blast Crisis - immunology; Candida albicans - immunology; Candidiasis - complications; Candidiasis - immunology; Candidiasis - microbiology; Care and treatment; Coculture Techniques; Cytokines - metabolism; Drug therapy; Female; Health aspects; Humans; Immunosuppression; Immunotherapy; Infection; Interferon-gamma - biosynthesis; Interleukin-10 - biosynthesis; Interleukin-17 - biosynthesis; Leukemia, Myeloid, Acute - blood; Leukemia, Myeloid, Acute - complications; Leukemia, Myeloid, Acute - immunology; Leukemia, Myeloid, Acute - microbiology; Lymphocyte Count; Male; Middle Aged; Myelocytic leukemia; Nonlymphoid leukemia; Sialic Acid Binding Ig-like Lectin 3 - metabolism; T cells; T-Lymphocytes - immunology; T-Lymphocytes, Helper-Inducer - immunology; Th17 Cells - immunology
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-015-0590-1

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.
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.
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.
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.