Tumor-derived granzyme B-expressing neutrophils acquire antitumor potential after lipid A treatment.
Fiche publication
Date publication
juin 2018
Journal
Oncotarget
Auteurs
Membres identifiés du Cancéropôle Est :
Dr ARNOULD Laurent, Pr BETTAIEB Ali, Pr PAUL Catherine
Tous les auteurs :
Martin A, Seignez C, Racoeur C, Isambert N, Mabrouk N, Scagliarini A, Reveneau S, Arnould L, Bettaieb A, Jeannin JF, Paul C
Lien Pubmed
Résumé
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.
Mots clés
colon cancer, granzyme B, immune response, lipid A, tumor-associated neutrophils
Référence
Oncotarget. 2018 Jun 19;9(47):28364-28378