@article{fc78063578304c6794c953296c872dbc,
title = "Tumor‐derived factors differentially affect the recruitment and plasticity of neutrophils",
abstract = "Neutrophils play a key role in cancer biology. In contrast to circulating normal‐density neutrophils (NDN), the amount of low‐density neutrophils (LDN) significantly increases with tumor progression. The correlation between these neutrophil subpopulations and intratumoral neutrophils (TANs) is still under debate. Using 4T1 (breast) and AB12 (mesothelioma) tumor models, we aimed to elucidate the source of TANs and to assess the mechanisms driving neutrophils{\textquoteright} plasticity in cancer. Both NDN and LDN were found to migrate in response to CXCL1 and CXCL2 exposure, and co‐infiltrate the tumor site ex vivo and in vivo, although LDN migration into the tumor was higher than NDN. Tumor‐derived factors and chemokines, particularly CXCL1, were found to drive neutrophil phenotypical plasticity, inducing NDN to transition towards a low‐density state (LD‐NDN). LD‐NDN appeared to differ from NDN by displaying a phenotypical profile similar to LDN in terms of nuclear morphology, surface receptor markers, decreased phagocytic abilities, and increased ROS production. Interestingly, all three subpopulations displayed comparable cytotoxic abilities towards tumor cells. Our data suggest that TANs originate from both LDN and NDN, and that a portion of LDN derives from NDN undergoing phenotypical changes. NDN plasticity resulted in a change in surface marker expression and functional activity, gaining characteristics of LDN.",
keywords = "CXCL1, CXCR2 and CXCR4, Cancer immunology, Cell plasticity, Neutrophils, cancer immunology, cell plasticity, neutrophils",
author = "Ludovica Arpinati and Naomi Kaisar‐iluz and Shaul, {Merav E.} and Christopher Groth and Viktor Umansky and Fridlender, {Zvi G.}",
note = "Funding Information: Funding: This research study was funded by the Sasson and Luisa Naor Fund (to Z.G.F.); the Co‐ operation Program in Cancer Research of the Deutsches Krebsforschungszentrum (DKFZ) and Is‐ rael{\textquoteright}s Ministry of Science and Technology (MOST) (to Z.G.F. and V.U.); the Israel Lung Association (to Z.G.F); and the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation), project number 259332240/RTG 2099 (to V.U.). Funding Information: This research study was funded by the Sasson and Luisa Naor Fund (to Z.G.F.); the Cooperation Program in Cancer Research of the Deutsches Krebsforschungszentrum (DKFZ) and Israel?s Ministry of Science and Technology (MOST) (to Z.G.F. and V.U.); the Israel Lung Association (to Z.G.F); and the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation), project number 259332240/RTG 2099 (to V.U.).The authors thank Prof. Z. Granot (The Hebrew University of Jerusalem, Israel) for providing the 4T1?luciferase cell line, as well as the Core Research Facility (CRF) at The Faculty of Medicine, The Hebrew University of Jerusalem. All schematic representations presented in the text, including the graphical abstract, were created using BioRender.com. Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).",
year = "2021",
month = oct,
day = "1",
doi = "https://doi.org/10.3390/cancers13205082",
language = "English",
volume = "13",
journal = "Cancers",
issn = "2072-6694",
publisher = "MDPI Multidisciplinary Digital Publishing Institute",
number = "20",
}
