Suppression of tumor-associated neutrophils by lorlatinib attenuates pancreatic cancer growth and improves treatment with immune checkpoint blockade

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 p...

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Bibliographic Details
Published in:	Nature communications Vol. 12; no. 1; pp. 3414 - 15
Main Authors:	Nielsen, Sebastian R., Strøbech, Jan E., Horton, Edward R., Jackstadt, Rene, Laitala, Anu, Bravo, Marina C., Maltese, Giorgia, Jensen, Adina R. D., Reuten, Raphael, Rafaeva, Maria, Karim, Saadia A., Hwang, Chang-Il, Arnes, Luis, Tuveson, David A., Sansom, Owen J., Morton, Jennifer P., Erler, Janine T.
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 07.06.2021 Nature Publishing Group Nature Portfolio
Subjects:	13/106 13/31 13/51 631/67/1504/1713 631/67/327 631/67/580 692/4028/67/580 96/95 Adenocarcinoma Aminopyridines Animal models Animals Antineoplastic Combined Chemotherapy Protocols - pharmacology Antineoplastic Combined Chemotherapy Protocols - therapeutic use Attenuation Cancer Carcinoma, Pancreatic Ductal - drug therapy Carcinoma, Pancreatic Ductal - pathology CD8 antigen CD8-Positive T-Lymphocytes - drug effects CD8-Positive T-Lymphocytes - immunology Cell Line, Tumor - transplantation Disease Models, Animal Drug Synergism Enzyme inhibitors Female Humanities and Social Sciences Humans Immune checkpoint Immune Checkpoint Inhibitors - pharmacology Immune Checkpoint Inhibitors - therapeutic use Immune system Kinases Lactams Lactams, Macrocyclic - pharmacology Lactams, Macrocyclic - therapeutic use Leukocytes (neutrophilic) Lymphocyte Activation - drug effects Lymphocytes Lymphocytes T Lymphocytes, Tumor-Infiltrating - drug effects Lymphocytes, Tumor-Infiltrating - immunology Male Medical prognosis Mice Mice, Transgenic multidisciplinary Neutrophils Neutrophils - drug effects Neutrophils - immunology Pancreatic cancer Pancreatic Neoplasms - drug therapy Pancreatic Neoplasms - genetics Pancreatic Neoplasms - immunology Pancreatic Neoplasms - pathology Patients PD-1 protein Prognosis Programmed Cell Death 1 Receptor - antagonists & inhibitors Programmed Cell Death 1 Receptor - metabolism Protein-tyrosine kinase Pyrazoles Science Science (multidisciplinary) Survival Tumor microenvironment Tumor Microenvironment - drug effects Tumor Microenvironment - immunology Tumors Tyrosine
ISSN:	2041-1723, 2041-1723
Online Access:	Get full text
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