2023-24-project-catalogue

###proton therapy and immune response in precision cut liver slices and tumours

Project ID: 2228bd1147 (You will need this ID for your application)

Research Theme: Healthcare Technologies

UCL Lead department: Cancer Institute

Department Website

Lead Supervisor: Maria Hawkins

Project Summary:

Radiation therapy is a common treatment for solid tumours by inducing cell DNA damage such as single strand, double strand and inter-strand cross links. DNA double strand breaks (DSBs) are the most lethal of these lesions. 40% of cancers are cured by radiation. Protons are charged particles that strongly interact with tissue and cause DNA damage. Compared with conventional X-ray based radiotherapy, protons have physical characteristics that result in a distinct dose deposition profile. Our research group has developed a robust, semi-automated pipeline to measure radiation-induced DNA damage by γH2AX and the production of reactive oxygen species (ROS) inhuman derived PCLS, related to the radiation dose received by the tissue. The student will characterise any difference in PBT radiosensitivity of liver tissues from humans and associated tumours ( metastases). Radiotherapy treatment has been used as an immunological adjuvant by reinvigorating an immune response towards cancer cells through immunogenic cell death (ICD; calreticulin expression and the release of HMGB1 and ATP into the tumour microenvironment). Dendritic cells ‘eat up’ the dying cancer cells and subsequently express their tumour cell antigens for cross priming and activation of cytotoxic CD8+ T cells. PBT has the potential to drive greater ICD responses than conventional X-ray radiotherapy, through an enhanced radiobiological effect at the proton Bragg peak. However, the radiation dose and fractionation patterns, important factors in manifesting a proportional ICD response in tumour cells, have not been fully studied or criticised. The student will investigate cancer and immune cell specific responses differ between protons and photons and possible implications for combination treatments. we are looking for an enthusiastic student who has some wet lab experience and can code