Macrophage and neutrophil interactions in the pancreatic tumor microenvironment drive the pathogenesis of pancreatic cancer

Pratt, Hillary G., Steinberger, Kayla J., Mihalik, Nicole E., Ott, Sascha, Whalley, Thomas, Szomolay, Barbara ORCID: https://orcid.org/0000-0002-5375-5533, Boone, Brian A. and Eubank, Timothy D. 2021. Macrophage and neutrophil interactions in the pancreatic tumor microenvironment drive the pathogenesis of pancreatic cancer. Cancers 14 (1) , 194. 10.3390/cancers14010194

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Abstract

Despite modest improvements in survival in recent years, pancreatic adenocarcinoma remains a deadly disease with a 5-year survival rate of only 9%. These poor outcomes are driven by failure of early detection, treatment resistance, and propensity for early metastatic spread. Uncovering innovative therapeutic modalities to target the resistance mechanisms that make pancreatic cancer largely incurable are urgently needed. In this review, we discuss the immune composition of pancreatic tumors, including the counterintuitive fact that there is a significant inflammatory immune infiltrate in pancreatic cancer yet anti-tumor mechanisms are subverted and immune behaviors are suppressed. Here, we emphasize how immune cell interactions generate tumor progression and treatment resistance. We narrow in on tumor macrophage (TAM) spatial arrangement, polarity/function, recruitment, and origin to introduce a concept where interactions with tumor neutrophils (TAN) perpetuate the microenvironment. The sequelae of macrophage and neutrophil activities contributes to tumor remodeling, fibrosis, hypoxia, and progression. We also discuss immune mechanisms driving resistance to standard of care modalities. Finally, we describe a cadre of treatment targets, including those intended to overcome TAM and TAN recruitment and function, to circumvent barriers presented by immune infiltration in pancreatic adenocarcinoma.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Medicine Biosciences
Additional Information:	This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/
Publisher:	MDPI
ISSN:	2072-6694
Date of First Compliant Deposit:	14 March 2022
Date of Acceptance:	28 December 2021
Last Modified:	03 May 2023 08:15
URI:	https://orca.cardiff.ac.uk/id/eprint/148356

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