42P - Investigating the immunogenic potential of radiation-induced cancer cell death

Date 05 November 2016
Event ESMO Symposium on Immuno-Oncology 2016
Session Lunch and general poster viewing
Presenter Claire Donaghy
Citation Annals of Oncology (2016) 27 (suppl_8): viii4-viii17. 10.1093/annonc/mdw527
Authors C. Donaghy
  • Postgraduate Education And Research Centre, Wythenshawe Hospital-South Manchester University Hospitals Trust, M23 9LT - Manchester/GB



Recent years have seen a paradigm shift with regard to the immunogenic profiles of cell death pathways involved in the demise of malignant cells. The discovery of immunogenic subroutines of apoptosis in response to certain antineoplastic therapies such as anthracyclines and ɣ-radiation in particular has made the prospect of aiding the patient’s own immune system to mount a robust cognate anti-tumour response a distinct and exciting possibility. This process has been suggested to be dependent upon the release of damage-associated molecular patterns (DAMPs). As such, combining inducers of immunogenic cell death (ICD) with immunotherapy may thus be particularly effective. In order to realise the goal of developing therapies which recruit the patient’s own immune system to eliminate all malignant cells, it will be crucial to delineate the prerequisites of an ICD phenotype.


To this end, we utilised the EL4 syngeneic murine T-cell thymoma cell line to compare the immunogenic profile of pure, classical apoptosis with that induced by external beam radiation therapy (RT), with particular focus on the release of HMGB1, a DAMP whose release is an obligate requirement for ICD. This was realised through the employment of cell death assays, cell staining using annexin V and propidium iodide and subsequent analysis by flow cytometry. Proteins released were visualised as immunoreactive bands using Western Blot.


In so doing we have demonstrated that the kinetics of cell death following RT differ from that of classical apoptosis. In addition, it was demonstrated that HMGB1 release following RT may be as a result of a previously undescribed biphasic mechanism dependent upon the activation of caspase-3 and ROCK1, indicating that membrane blebbing or autophagy may facilitate this release.


It is our hope that these data will aid the future planning of in vivo experiments in which the ICD phenotype may be further characterised, and provide rationale for the development of novel anti-cancer combination therapies.

Clinical trial identification

Laboratory-based research. No clinical trial protocol number available.

Legal entity responsible for the study

The University of Manchester


The University of Manchester


The author has declared no conflicts of interest.