Tumor-neutrophil crosstalk promotes in vitro and in vivo glioblastoma progression.

Introduction: 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. Methods: Using in vitro and in vivo assays, we demonstrate the existence of bidirectional GB and neutrophil communication, directly promoting an immunosuppressive TME. Results and discussion: 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-1ß, and IL-10 are associated with poor outcomes in patients with GB. Conclusion: These results are relevant for understanding how tumor progression occurs and how immune cells can help in this process.

The Impact of Mesenchymal Stromal Cells on Neutrophils: A Concise Review.

This review describes the current state of knowledge concerning interactions between mesenchymal stromal cells (MSCs) and neutrophils. MSCs are known as somatic multipotent cells with regenerative and anti-inflammatory abilities and immunomodulatory effects over other immune cells. Several studies reported that MSCs could affect the function and viability of neutrophils in their recruitment, activation, activity, survival, production of reactive oxygen species, phagocytosis capacity, and apoptosis. Moreover, neutrophils could be involved in the pro-metastatic effects of MSCs. Inversally, only a few studies pointed to the possibility of the opposite effect of neutrophils on MSCs. Understanding the interactions between MSCs and neutrophils could help promote therapeutic strategies using stromal cell-based therapeutic approaches, especially for hyper-immune pathologies, immunodeficiencies, and infectious diseases. However, further in vitro and in vivo studies are essential to determine the complete mechanisms of MSCs and neutrophils interaction.