Interleukin-17A Promotes the Growth of Human Germinal Center Derived Non-Hodgkin B Cell Lymphoma

Overview

Journal Oncoimmunology

Specialty Allergy & Immunology

Date 2015 Oct 10

PMID 26451300

Citations 14

Authors

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

Affiliations

Soon will be listed here.

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 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 proliferation of primary B-NHL cells; (vi) IL-17A (1 μg/mouse-per dose) stimulated B-NHL growth in two 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.

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References

Garrone P, Neidhardt E, Garcia E, Galibert L, van Kooten C, Banchereau J . Fas ligation induces apoptosis of CD40-activated human B lymphocytes. J Exp Med. 1995; 182(5):1265-73. PMC: 2192208. DOI: 10.1084/jem.182.5.1265. View

Tartour E, Fossiez F, Joyeux I, Galinha A, Gey A, Claret E . Interleukin 17, a T-cell-derived cytokine, promotes tumorigenicity of human cervical tumors in nude mice. Cancer Res. 1999; 59(15):3698-704. View

Ferretti E, Di Carlo E, Cocco C, Ribatti D, Sorrentino C, Ognio E . Direct inhibition of human acute myeloid leukemia cell growth by IL-12. Immunol Lett. 2010; 133(2):99-105. DOI: 10.1016/j.imlet.2010.08.002. View

MacLennan I . Germinal centers. Annu Rev Immunol. 1994; 12:117-39. DOI: 10.1146/annurev.iy.12.040194.001001. View

Vangsted A, Klausen T, Abildgaard N, Andersen N, Gimsing P, Gregersen H . Single nucleotide polymorphisms in the promoter region of the IL1B gene influence outcome in multiple myeloma patients treated with high-dose chemotherapy independently of relapse treatment with thalidomide and bortezomib. Ann Hematol. 2011; 90(10):1173-81. DOI: 10.1007/s00277-011-1194-3. View

Allen C, Okada T, Cyster J . Germinal-center organization and cellular dynamics. Immunity. 2007; 27(2):190-202. PMC: 2242846. DOI: 10.1016/j.immuni.2007.07.009. View

Allen C, Ansel K, Low C, Lesley R, Tamamura H, Fujii N . Germinal center dark and light zone organization is mediated by CXCR4 and CXCR5. Nat Immunol. 2004; 5(9):943-52. DOI: 10.1038/ni1100. View

Hata K, Andoh A, Shimada M, Fujino S, Bamba S, Araki Y . IL-17 stimulates inflammatory responses via NF-kappaB and MAP kinase pathways in human colonic myofibroblasts. Am J Physiol Gastrointest Liver Physiol. 2002; 282(6):G1035-44. DOI: 10.1152/ajpgi.00494.2001. View

Toy D, Kugler D, Wolfson M, Vanden Bos T, Gurgel J, Derry J . Cutting edge: interleukin 17 signals through a heteromeric receptor complex. J Immunol. 2006; 177(1):36-9. DOI: 10.4049/jimmunol.177.1.36. View

10.

Jain P, Javdan M, Feger F, Chiu P, Sison C, Damle R . Th17 and non-Th17 interleukin-17-expressing cells in chronic lymphocytic leukemia: delineation, distribution, and clinical relevance. Haematologica. 2011; 97(4):599-607. PMC: 3347674. DOI: 10.3324/haematol.2011.047316. View

11.

Leich E, Salaverria I, Bea S, Zettl A, Wright G, Moreno V . Follicular lymphomas with and without translocation t(14;18) differ in gene expression profiles and genetic alterations. Blood. 2009; 114(4):826-34. PMC: 2716022. DOI: 10.1182/blood-2009-01-198580. View

12.

Blaho V, Buczynski M, Dennis E, Brown C . Cyclooxygenase-1 orchestrates germinal center formation and antibody class-switch via regulation of IL-17. J Immunol. 2009; 183(9):5644-53. PMC: 2857380. DOI: 10.4049/jimmunol.0901499. View

13.

Victora G, Nussenzweig M . Germinal centers. Annu Rev Immunol. 2012; 30:429-57. DOI: 10.1146/annurev-immunol-020711-075032. View

14.

Benchetrit F, Ciree A, Vives V, Warnier G, Gey A, Sautes-Fridman C . Interleukin-17 inhibits tumor cell growth by means of a T-cell-dependent mechanism. Blood. 2002; 99(6):2114-21. DOI: 10.1182/blood.v99.6.2114. View

15.

Galand C, Donnou S, Crozet L, Brunet S, Touitou V, Ouakrim H . Th17 cells are involved in the local control of tumor progression in primary intraocular lymphoma. PLoS One. 2011; 6(9):e24622. PMC: 3176763. DOI: 10.1371/journal.pone.0024622. View

16.

Doreau A, Belot A, Bastid J, Riche B, Trescol-Biemont M, Ranchin B . Interleukin 17 acts in synergy with B cell-activating factor to influence B cell biology and the pathophysiology of systemic lupus erythematosus. Nat Immunol. 2009; 10(7):778-85. DOI: 10.1038/ni.1741. View

17.

Lafarge S, Hamzeh-Cognasse H, Chavarin P, Genin C, Garraud O, Cognasse F . A flow cytometry technique to study intracellular signals NF-kappaB and STAT3 in peripheral blood mononuclear cells. BMC Mol Biol. 2007; 8:64. PMC: 1949834. DOI: 10.1186/1471-2199-8-64. View

18.

Algood H, Allen S, Washington M, Peek Jr R, Miller G, Cover T . Regulation of gastric B cell recruitment is dependent on IL-17 receptor A signaling in a model of chronic bacterial infection. J Immunol. 2009; 183(9):5837-46. PMC: 2834183. DOI: 10.4049/jimmunol.0901206. View

19.

Mitsdoerffer M, Lee Y, Jager A, Kim H, Korn T, Kolls J . Proinflammatory T helper type 17 cells are effective B-cell helpers. Proc Natl Acad Sci U S A. 2010; 107(32):14292-7. PMC: 2922571. DOI: 10.1073/pnas.1009234107. View

20.

Corcione A, Ottonello L, Tortolina G, Facchetti P, Airoldi I, Guglielmino R . Stromal cell-derived factor-1 as a chemoattractant for follicular center lymphoma B cells. J Natl Cancer Inst. 2000; 92(8):628-35. DOI: 10.1093/jnci/92.8.628. View