Radiotherapy, Inflammation and Cancer: Exploring the Impacts of Radiotherapy on Skin Cancer Progression in Zebrafish
Lead Research Organisation:
University of Bristol
Department Name: Biochemistry
Abstract
Inflammation, and the subsequent action of innate immune cells is now widely appreciated to contribute to cancer progression; so much so, that immune infiltration and the release of pro-inflammatory signals correlates with enhanced tumour invasivion and poor clinical outcomes.
During cancer treatment, surgery and radiotherapy are routinely offered to patients as highly effective curative or palliative strategies. However, these approaches generate acute damage and as a consequence, enhance inflammation at the tumour site. There is rather little understanding of how external damage to tumours or their surrounding stroma alters the inflammatory landscape and how this influences immune behavior towards tumour cells in the days and weeks following therapy.
Live imaging studies in zebrafish in the Martin laboratory have modelled the impacts of surgery on cancer progression. It was revealed that wounds rapidly attract innate immune cells, namely neutrophils, towards the site of damage. However, these recruited immune cells were subsequently redirected towards nearby cancer cells, where they released trophic signals and fueled pre-neoplastic cell growth. This demonstrated that cancer therapies aren't without their costs.
Much like surgery, radiotherapy is another highly utilised and effective cancer therapy which causes damage and inflammation; yet it is unknown whether this too impacts cancer progression. This project will investigate precisely how radiotherapy influences the inflammatory response; and how this, in turn, might positively or negatively affect cancer progression.
This project will then use targeted radiotherapy on adult tumours in zebrafish to model clinical radiotherapy. In particular, I will live image DNA damage, cell death triggered by radiotherapy and how this damage manifests and drives inflammation, and how this influences subsequent cancer progression. Using this model for example it will be possible, for the first time to live image how innate and adaptive immune cells might mediate the abscopal effect. Over the past 50 years, clinicians have reported how that irradiation of one tumour can hinder the growth of nearby untreated tumours though the mechanism behind this phenonium is poorly understood. Using existing transgenic zebrafish at the University of Bristol, movement of various immune cell linages from an irradiated tumour to an unirradiated one could be tracked to identify whether recruited immune cells help or hinder tumour growth and visualise, for the first time, whether there is an immune component behind the poorly understood, yet clinically significant abscopal effect.
My project will also investigate what are the "damage" signals that are released from unwounded and from irradiated tumours including High Mobility Group Box Protein 1 (HMGB1) and how it might influence the cancer inflammatory response.
During cancer treatment, surgery and radiotherapy are routinely offered to patients as highly effective curative or palliative strategies. However, these approaches generate acute damage and as a consequence, enhance inflammation at the tumour site. There is rather little understanding of how external damage to tumours or their surrounding stroma alters the inflammatory landscape and how this influences immune behavior towards tumour cells in the days and weeks following therapy.
Live imaging studies in zebrafish in the Martin laboratory have modelled the impacts of surgery on cancer progression. It was revealed that wounds rapidly attract innate immune cells, namely neutrophils, towards the site of damage. However, these recruited immune cells were subsequently redirected towards nearby cancer cells, where they released trophic signals and fueled pre-neoplastic cell growth. This demonstrated that cancer therapies aren't without their costs.
Much like surgery, radiotherapy is another highly utilised and effective cancer therapy which causes damage and inflammation; yet it is unknown whether this too impacts cancer progression. This project will investigate precisely how radiotherapy influences the inflammatory response; and how this, in turn, might positively or negatively affect cancer progression.
This project will then use targeted radiotherapy on adult tumours in zebrafish to model clinical radiotherapy. In particular, I will live image DNA damage, cell death triggered by radiotherapy and how this damage manifests and drives inflammation, and how this influences subsequent cancer progression. Using this model for example it will be possible, for the first time to live image how innate and adaptive immune cells might mediate the abscopal effect. Over the past 50 years, clinicians have reported how that irradiation of one tumour can hinder the growth of nearby untreated tumours though the mechanism behind this phenonium is poorly understood. Using existing transgenic zebrafish at the University of Bristol, movement of various immune cell linages from an irradiated tumour to an unirradiated one could be tracked to identify whether recruited immune cells help or hinder tumour growth and visualise, for the first time, whether there is an immune component behind the poorly understood, yet clinically significant abscopal effect.
My project will also investigate what are the "damage" signals that are released from unwounded and from irradiated tumours including High Mobility Group Box Protein 1 (HMGB1) and how it might influence the cancer inflammatory response.
Organisations
People |
ORCID iD |
| Paul Martin (Primary Supervisor) | |
| Luke Deane (Student) |
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| MR/N013794/1 | 01/10/2016 | 30/09/2025 | |||
| 2131892 | Studentship | MR/N013794/1 | 01/10/2018 | 31/03/2022 | Luke Deane |