TLR2 Activation Promotes Tumour Growth and Associates with Patient Survival and Chemotherapy Response in Pancreatic Ductal Adenocarcinoma

Overview

Journal Oncogene

Specialties Molecular Biology
Oncology

Date 2021 Aug 17

PMID 34400766

Citations 9

Authors

Joanne Lundy

Linden J Gearing

Hugh Gao

Alison C West

Louise McLeod

Virginie Deswaerte

Liang Yu

Sean Porazinski

Marina Pajic

Paul J Hertzog

Daniel Croagh

Brendan J Jenkins

Affiliations

Soon will be listed here.

Abstract

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.

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