Investigating radiotherapy-induced immunogenic cell death in lymphomas

Abstract

Radiotherapy (RT) and chemotherapy are standard treatments for the majority of cancers. In addition to direct cytotoxic effects, some chemotherapeutic drugs, specifically anthracyclines as well as certain doses of external-beam ionising RT, generate tumour-specific immunity including induction of immunogenic cell death (ICD). ICD is a type of caspase-dependent cell death characterised by the release of damage associated molecular patterns (DAMP) which can prime CD8 T-cells. Despite immunogenic cell death having been proven to play a role in eliciting immune responses in the context of solid malignancies, little is known about the immunogenicity of such treatments, especially RT, in lymphomas. Therefore, this study aims to investigate whether RT can induce ICD in a range of murine lymphoma cell lines. A range of in vitro assays (flow cytometry, immunoblot, luminescence and electron microscopy) allowed characterization of the immunogenic phenotype (DAMP release). In vitro and in situ vaccination studies determined immunogenic potential of RT. Results determined that RT can induce DAMP release but not ICD as defined by vaccination studies nor activation of immune response in established lymphoma tumours. However, RT can induce ICD in a murine model of colorectal cancer. These results suggest that DAMP release may not be the sole determinant of immunogenicity of RT-induced cell death, and that additional intrinsic characteristics of tumour cells may dictate the ability to generate a tumour-specific immune response following treatment.

Date of Award	1 Aug 2020
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Timothy Illidge (Supervisor) & Jamie Honeychurch (Supervisor)