AUTHOR=Rubenich Dominique S. , de Souza Priscila O. , Omizzollo Natalia , Aubin Mariana R. , Basso Paulo J. , Silva Luisa M.  , da Silva Eloisa M. , Teixeira Fernanda C. , Gentil Gabriela F.S. , Domagalski Jordana L. , Cunha Maico T. , Gadelha Kerolainy A. , Diel Leonardo F. , Gelsleichter Nicolly E. , Rubenich Aline S. , Lenz Gabriela S. , de Abreu Aline M. , Kroeff Giselle M. , Paz Ana H. , Visioli Fernanda , Lamers Marcelo L. , Wink Marcia R. , Worm Paulo V. , Araújo Anelise B. , Sévigny Jean , Câmara Niels O. S. , Ludwig Nils , Braganhol Elizandra 

TITLE=Tumor-neutrophil crosstalk promotes in vitro and in vivo glioblastoma progression

JOURNAL=Frontiers in Immunology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1183465

DOI=10.3389/fimmu.2023.1183465

ISSN=1664-3224

ABSTRACT=<sec><title>Introduction</title><p>The tumor microenvironment (TME) of glioblastoma (GB) is characterized by an increased infiltration of immunosuppressive cells that attenuate the antitumor immune response. The participation of neutrophils in tumor progression is still controversial and a dual role in the TME has been proposed. In this study, we show that neutrophils are reprogrammed by the tumor to ultimately promote GB progression.</p></sec><sec><title>Methods</title><p>Using <italic>in vitro</italic> and <italic>in vivo</italic> assays, we demonstrate the existence of bidirectional GB and neutrophil communication, directly promoting an immunosuppressive TME. </p></sec><sec><title>Results and discussion</title><p>Neutrophils have shown to play an important role in tumor malignancy especially in advanced 3D tumor model and Balb/c nude mice experiments, implying a time- and neutrophil concentration-dependent modulation. Studying the tumor energetic metabolism indicated a mitochondria mismatch shaping the TME secretome. The given data suggests a cytokine milieu in patients with GB that favors the recruitment of neutrophils, sustaining an anti-inflammatory profile which is associated with poor prognosis. Besides, glioma-neutrophil crosstalk has sustained a tumor prolonged activation via NETs formation, indicating the role of NFκB signaling in tumor progression. Moreover, clinical samples have indicated that neutrophil-lymphocyte ratio (NLR), IL-1β, and IL-10 are associated with poor outcomes in patients with GB. </p></sec><sec><title>Conclusion</title><p>These results are relevant for understanding how tumor progression occurs and how immune cells can help in this process.</p></sec>