Journal article

Inhibition of PAK1 suppresses pancreatic cancer by stimulation of anti-tumour immunity through down-regulation of PD-L1

Kai Wang, Yifan Zhan, Huynh Nhi, Chelsea Dumesny, Xiao Wang, Khashayer Asadi, David Herrmann, Paul Timpson, Yang Yang, Katrina Walsh, Graham S Baldwin, Mehrdad Nikfarjam, Hong He

Cancer Letters | ELSEVIER IRELAND LTD | Published : 2020

Abstract

Immunotherapies have not yielded significant clinical benefits for pancreatic ductal adenocarcinoma (PDA) because of the existence of an immunosuppressive tumour microenvironment (TME) characterized by a desmoplastic stroma containing infiltrated immune cells and activated pancreatic stellate cells (PSCs). This study aims to investigate the involvement of PAK1 in anti-tumour immunity. In PDA patients, low PAK1 expression, low activation of PSC and high CD8+ T cell/PAK1 ratios correlated with longer overall survival. In a murine PDA model, PAK1 knockout increased intra-tumoral CD4+ and CD8+ T cells, inhibited PSCs activation and extended survival. Inhibition of PAK1 reduced PSC-stimulated PDA..

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Grants

Awarded by Austin Medical Research Foundation


Funding Acknowledgements

This work was supported by the Austin Medical Research Foundation (He-2019), the Tour de Cure Charity (https://www.tourdecure.com.au) and the Pancare Foundation (https://www.pancare.org.au).Kai Wang was supported by a Melbourne International Fee Remission Scholarship, a Melbourne International Research Scholarship, and the Moshe Sambor Scholarship (Pancare Foundation).