Tumor-derived granzyme B-expressing neutrophils acquire antitumor potential after lipid A treatment

Amandine Martin 1 Cédric Seignez 1 Cindy Racoeur 1 Nicolas Isambert 1, 2 Nesrine Mabrouk 1 Alessandra Scagliarini 1 Sylvie Reveneau 1 Laurent Arnould 2 Ali Bettaïeb 1 Jean-François Jeannin 1 Catherine Paul 1, *
* Auteur correspondant
1 LIIC - Laboratoire d'Immunologie et d'Immunothérapie des cancers [Dijon]
2 CRLCC - CGFL - Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc
Abstract : Neutrophils are known to possess both pro- and anti-tumor properties, a feature that could be related to the diversity and plasticity of these cells. Here we explored the hypothesis that under an appropriate environment and stimuli, neutrophils could induce an effective response against tumor cells. In a rat and mouse models, we show that a substantial amount of colon tumor associated-neutrophils (TAN) expressed the cytolytic enzyme granzyme B, which is absent in spleen or blood circulating neutrophils. This TAN population was also found into tumors of patients with colon cancer. Tumor neutrophil infiltration was correlated with an increase of chemokines known to attract neutrophils in both rat models and patients. These cells were involved in a Lipid A analog-mediated colon tumor regression. Mechanistically, treating the rats with the Lipid A analog triggered granzyme B release from neutrophils in tumor cell vicinity, which was correlated to tumor regression. Alteration of granzyme B function in tumor cells decreased the cytotoxic effect of Lipid A in rat and mouse models. Granzyme B expression in neutrophils could be induced by the lipid A analog but also by some of the cytokines that were detected in the tumor microenvironment. These results identify a subpopulation of neutrophils expressing granzyme B that can act as a key player of lipid A-mediated colon cancer regression in rat and mouse models and the molecular mechanisms involved may provide novel approaches for human therapeutic intervention.
Keywords : colon cancer granzyme B immune response lipid A tumor-associated neutrophils
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https://hal-univ-bourgogne.archives-ouvertes.fr/hal-01936476
Contributeur : Lnc - Université de Bourgogne <>
Soumis le : mardi 27 novembre 2018 - 14:16:45
Dernière modification le : mercredi 28 novembre 2018 - 01:16:15

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Amandine Martin, Cédric Seignez, Cindy Racoeur, Nicolas Isambert, Nesrine Mabrouk, et al.. Tumor-derived granzyme B-expressing neutrophils acquire antitumor potential after lipid A treatment. Oncotarget, Impact journals, 2018, 9 (47), pp.28364-28378. ⟨10.18632/oncotarget.25342⟩. ⟨hal-01936476⟩

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