Donlon NE, Davern M, Sheppard A, O'Connell F, Moran B, Nugent TS, Heeran A, Phelan JJ, Bhardwaj A, Butler C, Ravi N, Donohoe CL, Lynam-Lennon N, Maher S, Reynolds JV, Lysaght J. Potential of damage associated molecular patterns in synergising radiation and the immune response in oesophageal cancer. World J Gastrointest Oncol 2023; 15(8): 1349-1365 [PMID: 37663943 DOI: 10.4251/wjgo.v15.i8.1349]
Corresponding Author of This Article
Noel E Donlon, MD, PhD, Assistant Professor, Cancer Immunology and Immunotherapy Group, Department of Surgery, Trinity Translational Medicine Institute and Trinity St James’s Cancer Institute, Trinity College Dublin, St James’s Hospital, James's Street Dublin 8, Dublin D08, Ireland. donlonn@tcd.ie
Research Domain of This Article
Immunology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastrointest Oncol. Aug 15, 2023; 15(8): 1349-1365 Published online Aug 15, 2023. doi: 10.4251/wjgo.v15.i8.1349
Potential of damage associated molecular patterns in synergising radiation and the immune response in oesophageal cancer
Noel E Donlon, Maria Davern, Andrew Sheppard, Fiona O'Connell, Brendan Moran, Timothy S Nugent, Aisling Heeran, James J Phelan, Anshul Bhardwaj, Christine Butler, Narayanasamy Ravi, Claire L Donohoe, Niamh Lynam-Lennon, Stephen Maher, John V Reynolds, Joanne Lysaght
Noel E Donlon, Maria Davern, Andrew Sheppard, Fiona O'Connell, Brendan Moran, Timothy S Nugent, Aisling Heeran, James J Phelan, Anshul Bhardwaj, Christine Butler, Narayanasamy Ravi, Claire L Donohoe, Niamh Lynam-Lennon, Stephen Maher, John V Reynolds, Joanne Lysaght, Cancer Immunology and Immunotherapy Group, Department of Surgery, Trinity Translational Medicine Institute and Trinity St James’s Cancer Institute, Trinity College Dublin, St James’s Hospital, Dublin D08, Ireland
Author contributions: Donlon NE and Davern M contributed equally to writing and experimentation; all other authors contributed to sample acquisition and data collection; Reynolds JV and Lysaght J contributed to supervision.
Institutional review board statement: This body of work was ethically approved by the SJH/TUH Ethics Committee.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Noel E Donlon, MD, PhD, Assistant Professor, Cancer Immunology and Immunotherapy Group, Department of Surgery, Trinity Translational Medicine Institute and Trinity St James’s Cancer Institute, Trinity College Dublin, St James’s Hospital, James's Street Dublin 8, Dublin D08, Ireland. donlonn@tcd.ie
Received: January 14, 2023 Peer-review started: January 14, 2023 First decision: March 14, 2023 Revised: March 29, 2023 Accepted: June 25, 2023 Article in press: June 25, 2023 Published online: August 15, 2023
Abstract
BACKGROUND
There is an intimate crosstalk between cancer formation, dissemination, treatment response and the host immune system, with inducing tumour cell death the ultimate therapeutic goal for most anti-cancer treatments. However, inducing a purposeful synergistic response between conventional therapies and the immune system remains evasive. The release of damage associated molecular patterns (DAMPs) is indicative of immunogenic cell death and propagation of established immune responses. However, there is a gap in the literature regarding the importance of DAMP expression in oesophageal adenocarcinoma (OAC) or by immune cells themselves.
AIM
To investigate the effects of conventional therapies on DAMP expression and to determine whether OAC is an immunogenic cancer.
METHODS
We investigated the levels of immunogenic cell death-associated DAMPs, calreticulin (CRT) and HMGB1 using an OAC isogenic model of radioresistance. DAMP expression was also assessed directly using ex vivo cancer patient T cells (n = 10) and within tumour biopsies (n = 9) both pre and post-treatment with clinically relevant chemo(radio)therapeutics.
RESULTS
Hypoxia in combination with nutrient deprivation significantly reduces DAMP expression by OAC cells in vitro. Significantly increased frequencies of T cell DAMP expression in OAC patients were observed following chemo(radio)therapy, which was significantly higher in tumour tissue compared with peripheral blood. Patients with high expression of HMGB1 had a significantly better tumour regression grade (TRG 1-2) compared to low expressors.
CONCLUSION
In conclusion, OAC expresses an immunogenic phenotype with two distinct subgroups of high and low DAMP expressors, which correlated with tumour regression grade and lymphatic invasion. It also identifies DAMPs namely CRT and HMGB1 as potential promising biomarkers in predicting good pathological responses to conventional chemo(radio)therapies currently used in the multimodal management of locally advanced disease.
Core Tip: The purpose of this study was to investigate the effects of conventional therapies on damage associated molecular patterns expression and we determined oesophageal adenocarcinoma is an immunogenic cancer and is a viable target for immunotherapeutics.
