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

K Wang; Y Zhan; N Huynh; C Dumesny; X Wang; K Asadi; D Herrmann; P Timpson; Y Yang; K Walsh; GS Baldwin; M Nikfarjam; H He

Journal article

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

K Wang, Y Zhan, N Huynh, C Dumesny, X Wang, K Asadi, D Herrmann, P Timpson, Y Yang, K Walsh, GS Baldwin, M Nikfarjam, H He

Cancer Letters | ELSEVIER IRELAND LTD | Published : 2020

DOI: 10.1016/j.canlet.2019.12.020

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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University of Melbourne Researchers

Yang Yang Author

Katrina Walsh Author

Mehrdad Nikfarjam Author

Hong He Author

Grants

Awarded by Pancare 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).