Oncotarget

Research Papers:

Neutrophils trigger a NF-κB dependent polarization of tumor-supportive stromal cells in germinal center B-cell lymphomas

Murielle Grégoire, Fabien Guilloton, Céline Pangault, Frédéric Mourcin, Phaktra Sok, Maelle Latour, Patricia Amé-Thomas, Erwan Flecher, Thierry Fest and Karin Tarte _

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Oncotarget. 2015; 6:16471-16487. https://doi.org/10.18632/oncotarget.4106

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Abstract

Murielle Grégoire1,2,3, Fabien Guilloton1,2,3, Céline Pangault1,2,3,4, Frédéric Mourcin1,2,3, Phaktra Sok1,2,3,5, Maelle Latour3,4, Patricia Amé-Thomas1,2,3,4, Erwan Flecher6, Thierry Fest1,2,3,4 and Karin Tarte1,2,3,4

1 INSERM, UMR U917, Equipe Labellisée Ligue Contre le Cancer, Rennes, France

2 Université Rennes 1, UMR917, Rennes, France

3 EFS Bretagne, Rennes, France

4 CHU de Rennes, Pôle Biologie, Rennes, France

CHU de Rennes, Service de Médecine de L’enfant et de L’adolescent, Rennes, France

6 CHU de Rennes, Service de Chirurgie Thoracique et Cardiovasculaire, Rennes, France

Correspondence to:

Karin Tarte, email:

Keywords: B-cell lymphoma, tumor microenvironment, cell interaction, cell differentiation, lymph node

Received: April 21, 2015 Accepted: April 23, 2015 Published: May 12, 2015

Abstract

Both tumor-associated neutrophils (TAN) and cancer-associated fibroblasts (CAFs) display specific phenotypic and functional features and contribute to tumor cell niche. However, their bidirectional crosstalk has been poorly studied, in particular in the context of hematological malignancies. Follicular lymphomas (FL) and diffuse large B-cell lymphomas (DLBCL) are two germinal center-derived lymphomas where various cell components of infiltrating microenvironment, including TAN and CAFs, have been demonstrated to favor directly and indirectly malignant B-cell survival, growth, and drug resistance. We show here that, besides a direct and contact-dependent supportive effect of neutrophils on DLBCL B-cell survival, mediated through the BAFF/APRIL pathway, neutrophils and stromal cells cooperate to sustain FL B-cell growth. This cooperation relies on an overexpression of IL-8 by lymphoma-infiltrating stromal cells that could thereafter efficiently promote neutrophil survival and prime them to neutrophil extracellular trap. Conversely, neutrophils are able to activate stromal cells in a NF-κB-dependent manner, inducing their commitment towards an inflammatory lymphoid stroma phenotype associated with an increased capacity to trigger malignant B-cell survival, and to recruit additional monocytes and neutrophils through the release of CCL2 and IL-8, respectively. Altogether, a better understanding of the lymphoma-supporting effects of neutrophils could be helpful to design new anti-tumor therapeutic strategies.


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PII: 4106