@article{ffa6be9b66094a78900e4adc15eb5dc0,
title = "Suppression of tumor-associated neutrophils by lorlatinib attenuates pancreatic cancer growth and improves treatment with immune checkpoint blockade",
abstract = "Pancreatic ductal adenocarcinoma (PDAC) patients have a 5-year survival rate of only 8% largely due to late diagnosis and insufficient therapeutic options. Neutrophils are among the most abundant immune cell type within the PDAC tumor microenvironment (TME), and are associated with a poor clinical prognosis. However, despite recent advances in understanding neutrophil biology in cancer, therapies targeting tumor-associated neutrophils are lacking. Here, we demonstrate, using pre-clinical mouse models of PDAC, that lorlatinib attenuates PDAC progression by suppressing neutrophil development and mobilization, and by modulating tumor-promoting neutrophil functions within the TME. When combined, lorlatinib also improves the response to anti-PD-1 blockade resulting in more activated CD8 + T cells in PDAC tumors. In summary, this study identifies an effect of lorlatinib in modulating tumor-associated neutrophils, and demonstrates the potential of lorlatinib to treat PDAC.",
author = "Nielsen, {Sebastian R.} and Str{\o}bech, {Jan E.} and Horton, {Edward R.} and Rene Jackstadt and Anu Laitala and Bravo, {Marina C.} and Giorgia Maltese and Jensen, {Adina R.D.} and Raphael Reuten and Maria Rafaeva and Karim, {Saadia A.} and Hwang, {Chang Il} and Luis Arnes and Tuveson, {David A.} and Sansom, {Owen J.} and Morton, {Jennifer P.} and Erler, {Janine T.}",
note = "Funding Information: We want to thank the Core Facilities at BRIC for their excellent assistance and the Biological Services Unit at the CRUK Beatson Institute. This work was supported by the Danish Cancer Society (S.R.N.: R167-A10618; E.R.H.: R204-A12445; R.R.: R204-A12454), the European Molecular Biology Organisation (E.R.H.: ALTF 922-2016), the European Research Council (S.R.N., E.R.H., J.E.S., A.M.L., A.R.D.J., R.R., and J.T.E.: ERC-2015-CoG-682881-Matrican), Cancer Research UK (R.J., S.A.K., J.P.M., and O.J.S.: A25142, A17196, A21139, and A25233), the German Cancer Aid (RR: 9166564), the National Institute of Health (C.I.H.: 1F32CA180717-01A1 and 5K22CA226037-02) and a Hallas-M{\o}ller Stipend from the Novo Nordisk Foundation (J.T.E.). Publisher Copyright: {\textcopyright} 2021, The Author(s).",
year = "2021",
month = dec,
doi = "10.1038/s41467-021-23731-7",
language = "English",
volume = "12",
pages = "1--15",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",
number = "1",
}