MILAN, Italy, February 1, 2023 – The Discovery Biology Unit at Dompé farmaceutici, in collaboration with Università degli Studi dell’Aquila, has published in December on Frontiers in Oncology a review of the literature in which describes a novel mechanism of cancer drug resistance mediated by neutrophils.
Neutrophils are one of the white cell types that act as the immune system’s first defense line. However, in some pathologies their activity can be twisted and they can become a treat promoting tumor progression and drug resistance. This happens in cancer where neutrophils’ behavior is modulated by different stimuli including the extracellular vesicles, specific vesicles released by cells that act as a cell-to-cell communication system, and interleukin-8, an important protein related to inflammation that attracts the neutrophils towards inflammatory sites.
Once recruited into the tumor, microenvironment neutrophils are called tumor-associated neutrophils or TANs, which are a plastic and dynamic population that can acquire immunoregulatory abilities that hijack the immune system response against the tumor contributing substantially to carcinogenesis. In this context the EVs are crucial since they can profoundly induce the reprogramming of recipient cells.
TANs can also regulate metastasization and drug resistance through NETosis, a process by which activated neutrophils extrude a sort of web-like structures of DNA fibers called NETs, that can act as a sort of shield of the tumor niche.
With this complex picture in mind, researchers investigated the role of EVs and IL-8 as key regulators of neutrophil behavior in cancer with an eye toward demonstrating the importance of developing novel drugs able to regulate neutrophil biology.