Publications Search

Search for publications by author
Search for publications by abstract keyword(s)

TLR2 activation promotes tumour growth and associates with patient survival and chemotherapy response in pancreatic ductal adenocarcinoma


Pancreatic ductal adenocarcinoma (PDAC) has an extremely poor prognosis, and is plagued by a paucity of targeted treatment options and tumour resistance to chemotherapeutics. The causal link between chronic inflammation and PDAC suggests that molecular regulators of the immune system promote disease pathogenesis and/or therapeutic resistance, yet their identity is unclear. Here, we couple endoscopic ultrasound-guided fine-needle aspiration, which captures tumour biopsies from all stages, with whole transcriptome profiling of PDAC patient primary tumours to reveal enrichment of the innate immune Toll-like receptor 2 (TLR2) molecular pathway. Augmented TLR2 expression associated with a 4-gene "TLR2 activation" signature, and was prognostic for survival and predictive for gemcitabine-based chemoresistance. Furthermore, antibody-mediated anti-TLR2 therapy suppressed the growth of human PDAC tumour xenografts, independent of a functional immune system. Our results support TLR2-based therapeutic targeting for precision medicine in PDAC, with further clinical utility that TLR2 activation is prognostic and predictive for chemoresponsiveness.

Type Journal
ISBN 1476-5594 (Electronic) 0950-9232 (Linking)
Authors Lundy, J.; Gearing, L. J.; Gao, H.; West, A. C.; McLeod, L.; Deswaerte, V.; Yu, L.; Porazinski, S.; Pajic, M.; Hertzog, P. J.; Croagh, D.; Jenkins, B. J.
Publisher Name ONCOGENE
Published Date 2021-10-31
Status Published in-print
DOI 10.1038/s41388-021-01992-2
URL link to publisher's version