Interleukin-17A promotes the growth of human germinal center derived non-Hodgkin B cell lymphoma

Elisa Ferretti, Emma Di Carlo, Emanuela Ognio, Carla Guarnotta, Francesco Bertoni, Anna Corcione, Ignazia Prigione, Giulio Fraternali-Orcioni, Domenico Ribatti, Jean Louis Ravetti, Maurilio Ponzoni, Claudio Tripodo, Vito Pistoia

Research output: Contribution to journalArticle

Abstract

Interleukin (IL)-17A belongs to IL-17 superfamily and binds the heterodimeric IL-17 receptor (R)(IL-17RA/IL-17RC). IL-17A promotes germinal center (GC) formation in mouse models of autoimmune or infectious diseases, but the role of IL-17A/IL-17AR complex in human neoplastic GC is unknown. In this study, we investigated expression and function of IL-17A/IL-17AR in the microenvironments of 44 B cell non-Hodgkin lymphomas (B-NHL) of GC origin (15 follicular lymphomas, 17 diffuse large B cells lymphomas and 12 Burkitt lymphomas) and 12 human tonsil GC. Furthermore, we investigated the role of IL-17A in two in vivo models of GC B cell lymphoma, generated by s.c. injection of SU-DHL-4 and OCI-Ly8 cell lines in Severe combined immunodeficiency (SCID)/Non Obese Diabetic (NOD) mice. We found that: (i) B-NHL cell fractions and tonsil GC B cells expressed IL-17RA/IL-17RC, (ii) IL-17A signaled in both cell types through NF-kBp65, but not p38, ERK-1/2, Akt or NF-kBp50/105, phosphorylation, (iii) IL-17A was expressed in T cells and mast cells from neoplastic and normal GC microenvironments, (iv) IL-17A rendered tonsil GC B cells competent to migrate to CXCL12 and CXCL13 by downregulating RGS16 expression; (v) IL-17A stimulated in vitro proliferation of primary B-NHL cells; (vi) IL-17A (1 μg/mouse-per dose) stimulated B-NHL growth in two in vivo models by enhancing tumor cell proliferation and neo-angiogenesis. This latter effect depended on IL-17A-mediated induction of pro-angiogenic gene expression in tumor cells and direct stimulation of endothelial cells. These data define a previously unrecognized role of human IL-17A in promoting growth of GC-derived B-NHL and modulating normal GC B cell trafficking.

Original languageEnglish
JournalOncoImmunology
Volume4
Issue number10
DOIs
Publication statusPublished - Oct 3 2015

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Germinal Center
Interleukin-17
B-Cell Lymphoma
Non-Hodgkin's Lymphoma
Interleukins
Growth
Palatine Tonsil
B-Lymphocytes
Interleukin-17 Receptors
Severe Combined Immunodeficiency
Inbred NOD Mouse
Follicular Lymphoma
Burkitt Lymphoma
Lymphoma, Large B-Cell, Diffuse
Mast Cells
Autoimmune Diseases
Communicable Diseases
Neoplasms
Down-Regulation
Endothelial Cells

Keywords

  • angiogenesis
  • B non-Hodgkin lymphoma
  • GC B cells
  • IL-17A
  • IL-17A receptor
  • tumor immunology

ASJC Scopus subject areas

  • Immunology and Allergy
  • Oncology
  • Immunology

Cite this

Interleukin-17A promotes the growth of human germinal center derived non-Hodgkin B cell lymphoma. / Ferretti, Elisa; Di Carlo, Emma; Ognio, Emanuela; Guarnotta, Carla; Bertoni, Francesco; Corcione, Anna; Prigione, Ignazia; Fraternali-Orcioni, Giulio; Ribatti, Domenico; Ravetti, Jean Louis; Ponzoni, Maurilio; Tripodo, Claudio; Pistoia, Vito.

In: OncoImmunology, Vol. 4, No. 10, 03.10.2015.

Research output: Contribution to journalArticle

Ferretti, E, Di Carlo, E, Ognio, E, Guarnotta, C, Bertoni, F, Corcione, A, Prigione, I, Fraternali-Orcioni, G, Ribatti, D, Ravetti, JL, Ponzoni, M, Tripodo, C & Pistoia, V 2015, 'Interleukin-17A promotes the growth of human germinal center derived non-Hodgkin B cell lymphoma', OncoImmunology, vol. 4, no. 10. https://doi.org/10.1080/2162402X.2015.1030560
Ferretti, Elisa ; Di Carlo, Emma ; Ognio, Emanuela ; Guarnotta, Carla ; Bertoni, Francesco ; Corcione, Anna ; Prigione, Ignazia ; Fraternali-Orcioni, Giulio ; Ribatti, Domenico ; Ravetti, Jean Louis ; Ponzoni, Maurilio ; Tripodo, Claudio ; Pistoia, Vito. / Interleukin-17A promotes the growth of human germinal center derived non-Hodgkin B cell lymphoma. In: OncoImmunology. 2015 ; Vol. 4, No. 10.
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AU - Ribatti, Domenico

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AU - Pistoia, Vito

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