Volume 2 Supplement 2

Abstracts from the 1st Immunotherapy of Cancer Conference (ITOC1)

Open Access

P17. RIG-I-like helicases induce immunogenic cell death of pancreatic cancer cells

  • M Schnurr1,
  • A Steger2,
  • H Lohr2,
  • H Bourhis2,
  • S Endres2 and
  • P Duewell2
Journal for ImmunoTherapy of Cancer20142(Suppl 2):P8

DOI: 10.1186/2051-1426-2-S2-P8

Published: 12 March 2014

Background

We recently identified RIG-I-like helicases (RLH) as therapeutic targets of pancreatic cancer for counteracting immunosuppressive mechanisms and apoptosis induction. Here, we investigated immunogenic consequences of RLH-induced tumour cell death.

Material and methods

Murine pancreatic cancer cells (Panc02) were treated with RLH ligands to induce apoptosis and were then cocultured with primary dendritic cells (DC). DC maturation marker expression, antigen uptake and antigen cross-presentation were assessed.

Results

RLH ligands induced production of type I IFN, HMGB1 and Hsp70 and translocation of calreticulin to the outer cell membrane of tumour cells. In cocultures, DC upregulated B7 expression, which was mediated by tumour-derived type I IFN, whereas TLR, RAGE or inflammasome signaling was dispensable. CD8a+ DC effectively engulfed apoptotic tumour material and cross-presented tumour-associated antigen to naïve CD8+ T cells. In comparison, tumour cell death mediated by oxaliplatin, staurosporine or mechanical disruption failed to induce DC activation, antigen uptake or cross-presentation. Moreover, tumour cells treated with sublethal doses of RLH ligands upregulated MHC-I and Fas expression and were sensitised towards CTL- and Fas-mediated killing.

Conclusions

RLH ligands induce a highly immunogenic form of tumour cell death linking innate and adaptive immunity.

Authors’ Affiliations

(1)
Division of Clinical Pharmacology
(2)
LMU Munich, Division of Clinical Pharmacology

Copyright

© Schnurr et al; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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