IL-25 dampens the growth of human germinal center-derived B-cell non Hodgkin Lymphoma by curtailing neoangiogenesis

Elisa Ferretti, Emma Di Carlo, Emanuela Ognio, Giulio Fraternali-Orcioni, Anna Corcione, Beatrice Belmonte, Jean Louis Ravetti, Claudio Tripodo, Domenico Ribatti, Vito Pistoia

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Abstract

Interleukin (IL)-25, a member of the IL-17 cytokine superfamily, is produced by immune and non-immune cells and exerts type 2 pro-inflammatory effectsin vitroandin vivo. The IL-25 receptor(R) is composed of the IL-17RA/IL-17RB subunits. Previous work showed that germinal centre (GC)-derived B-cell non Hodgkin lymphomas (B-NHL) expressed IL-17AR, formed by IL-17RA and IL-17RC subunits, and IL-17A/IL-17AR axis promoted B-NHL growth by stimulating neoangiogenesis. Here, we have investigated expression and function of IL-25/IL-25R axis in lymph nodes from human GC-derived B-NHL, i.e. Follicular Lymphoma (FL,10 cases), Diffuse Large B Cell Lymphoma (6 cases) and Burkitt Lymphoma (3 cases). Tumor cells expressed IL-25R and IL-25 that was detected also in non-malignant cells by flow cytometry. Immunohistochemical studies confirmed expression of IL-25R and IL-25 in FL cells, and highlighted IL-25 expression in bystander elements of the FL microenvironment. IL-25 i) up-regulated phosphorylation of NFkBp65, STAT-1 and JNK in B-NHL cells; ii) inhibitedin vitroproliferation of the latter cells; iii) exerted anti-tumor activity in twoin vivoB-NHL models by dampening expression of pro-angiogenic molecules as VEGF-C, CXCL6 and ANGPT3. In conclusion, IL-25, that is intrinsically pro-angiogenic, inhibits B-NHL growth by reprogramming the angiogenic phenotype of B-NHL cells.

Original languageEnglish
Pages (from-to)e1397249
JournalOncoImmunology
Volume7
Issue number3
DOIs
Publication statusPublished - 2017

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Germinal Center
Interleukin-17
B-Cell Lymphoma
Interleukins
Non-Hodgkin's Lymphoma
Growth
Interleukin Receptors
Vascular Endothelial Growth Factor C
Follicular Lymphoma
Burkitt Lymphoma
Lymphoma, Large B-Cell, Diffuse
Neoplasms
Flow Cytometry
Lymph Nodes
Phosphorylation
Cytokines
Phenotype

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IL-25 dampens the growth of human germinal center-derived B-cell non Hodgkin Lymphoma by curtailing neoangiogenesis. / Ferretti, Elisa; Di Carlo, Emma; Ognio, Emanuela; Fraternali-Orcioni, Giulio; Corcione, Anna; Belmonte, Beatrice; Ravetti, Jean Louis; Tripodo, Claudio; Ribatti, Domenico; Pistoia, Vito.

In: OncoImmunology, Vol. 7, No. 3, 2017, p. e1397249.

Research output: Contribution to journalArticle

Ferretti, E, Di Carlo, E, Ognio, E, Fraternali-Orcioni, G, Corcione, A, Belmonte, B, Ravetti, JL, Tripodo, C, Ribatti, D & Pistoia, V 2017, 'IL-25 dampens the growth of human germinal center-derived B-cell non Hodgkin Lymphoma by curtailing neoangiogenesis', OncoImmunology, vol. 7, no. 3, pp. e1397249. https://doi.org/10.1080/2162402X.2017.1397249
Ferretti, Elisa ; Di Carlo, Emma ; Ognio, Emanuela ; Fraternali-Orcioni, Giulio ; Corcione, Anna ; Belmonte, Beatrice ; Ravetti, Jean Louis ; Tripodo, Claudio ; Ribatti, Domenico ; Pistoia, Vito. / IL-25 dampens the growth of human germinal center-derived B-cell non Hodgkin Lymphoma by curtailing neoangiogenesis. In: OncoImmunology. 2017 ; Vol. 7, No. 3. pp. e1397249.
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abstract = "Interleukin (IL)-25, a member of the IL-17 cytokine superfamily, is produced by immune and non-immune cells and exerts type 2 pro-inflammatory effectsin vitroandin vivo. The IL-25 receptor(R) is composed of the IL-17RA/IL-17RB subunits. Previous work showed that germinal centre (GC)-derived B-cell non Hodgkin lymphomas (B-NHL) expressed IL-17AR, formed by IL-17RA and IL-17RC subunits, and IL-17A/IL-17AR axis promoted B-NHL growth by stimulating neoangiogenesis. Here, we have investigated expression and function of IL-25/IL-25R axis in lymph nodes from human GC-derived B-NHL, i.e. Follicular Lymphoma (FL,10 cases), Diffuse Large B Cell Lymphoma (6 cases) and Burkitt Lymphoma (3 cases). Tumor cells expressed IL-25R and IL-25 that was detected also in non-malignant cells by flow cytometry. Immunohistochemical studies confirmed expression of IL-25R and IL-25 in FL cells, and highlighted IL-25 expression in bystander elements of the FL microenvironment. IL-25 i) up-regulated phosphorylation of NFkBp65, STAT-1 and JNK in B-NHL cells; ii) inhibitedin vitroproliferation of the latter cells; iii) exerted anti-tumor activity in twoin vivoB-NHL models by dampening expression of pro-angiogenic molecules as VEGF-C, CXCL6 and ANGPT3. In conclusion, IL-25, that is intrinsically pro-angiogenic, inhibits B-NHL growth by reprogramming the angiogenic phenotype of B-NHL cells.",
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AU - Ferretti, Elisa

AU - Di Carlo, Emma

AU - Ognio, Emanuela

AU - Fraternali-Orcioni, Giulio

AU - Corcione, Anna

AU - Belmonte, Beatrice

AU - Ravetti, Jean Louis

AU - Tripodo, Claudio

AU - Ribatti, Domenico

AU - Pistoia, Vito

PY - 2017

Y1 - 2017

N2 - Interleukin (IL)-25, a member of the IL-17 cytokine superfamily, is produced by immune and non-immune cells and exerts type 2 pro-inflammatory effectsin vitroandin vivo. The IL-25 receptor(R) is composed of the IL-17RA/IL-17RB subunits. Previous work showed that germinal centre (GC)-derived B-cell non Hodgkin lymphomas (B-NHL) expressed IL-17AR, formed by IL-17RA and IL-17RC subunits, and IL-17A/IL-17AR axis promoted B-NHL growth by stimulating neoangiogenesis. Here, we have investigated expression and function of IL-25/IL-25R axis in lymph nodes from human GC-derived B-NHL, i.e. Follicular Lymphoma (FL,10 cases), Diffuse Large B Cell Lymphoma (6 cases) and Burkitt Lymphoma (3 cases). Tumor cells expressed IL-25R and IL-25 that was detected also in non-malignant cells by flow cytometry. Immunohistochemical studies confirmed expression of IL-25R and IL-25 in FL cells, and highlighted IL-25 expression in bystander elements of the FL microenvironment. IL-25 i) up-regulated phosphorylation of NFkBp65, STAT-1 and JNK in B-NHL cells; ii) inhibitedin vitroproliferation of the latter cells; iii) exerted anti-tumor activity in twoin vivoB-NHL models by dampening expression of pro-angiogenic molecules as VEGF-C, CXCL6 and ANGPT3. In conclusion, IL-25, that is intrinsically pro-angiogenic, inhibits B-NHL growth by reprogramming the angiogenic phenotype of B-NHL cells.

AB - Interleukin (IL)-25, a member of the IL-17 cytokine superfamily, is produced by immune and non-immune cells and exerts type 2 pro-inflammatory effectsin vitroandin vivo. The IL-25 receptor(R) is composed of the IL-17RA/IL-17RB subunits. Previous work showed that germinal centre (GC)-derived B-cell non Hodgkin lymphomas (B-NHL) expressed IL-17AR, formed by IL-17RA and IL-17RC subunits, and IL-17A/IL-17AR axis promoted B-NHL growth by stimulating neoangiogenesis. Here, we have investigated expression and function of IL-25/IL-25R axis in lymph nodes from human GC-derived B-NHL, i.e. Follicular Lymphoma (FL,10 cases), Diffuse Large B Cell Lymphoma (6 cases) and Burkitt Lymphoma (3 cases). Tumor cells expressed IL-25R and IL-25 that was detected also in non-malignant cells by flow cytometry. Immunohistochemical studies confirmed expression of IL-25R and IL-25 in FL cells, and highlighted IL-25 expression in bystander elements of the FL microenvironment. IL-25 i) up-regulated phosphorylation of NFkBp65, STAT-1 and JNK in B-NHL cells; ii) inhibitedin vitroproliferation of the latter cells; iii) exerted anti-tumor activity in twoin vivoB-NHL models by dampening expression of pro-angiogenic molecules as VEGF-C, CXCL6 and ANGPT3. In conclusion, IL-25, that is intrinsically pro-angiogenic, inhibits B-NHL growth by reprogramming the angiogenic phenotype of B-NHL cells.

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DO - 10.1080/2162402X.2017.1397249

M3 - Article

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VL - 7

SP - e1397249

JO - OncoImmunology

JF - OncoImmunology

SN - 2162-4011

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ER -