Donlon NE, Davern M, O’Connell F, Sheppard A, Heeran A, Bhardwaj A, Butler C, Narayanasamy R, Donohoe C, Phelan JJ, Lynam-Lennon N, Dunne MR, Maher S, O’Sullivan J, Reynolds JV, Lysaght J. Impact of radiotherapy on the immune landscape in oesophageal adenocarcinoma. World J Gastroenterol 2022; 28(21): 2302-2319 [PMID: 35800186 DOI: 10.3748/wjg.v28.i21.2302]
Corresponding Author of This Article
Noel E Donlon, MD, Assistant Professor, Department of Surgery, Trinity Translational Medicine Institute, St James Hospital, James’s Street, Dublin D08, Ireland. donlonn@tcd.ie
Research Domain of This Article
Surgery
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 Gastroenterol. Jun 7, 2022; 28(21): 2302-2319 Published online Jun 7, 2022. doi: 10.3748/wjg.v28.i21.2302
Impact of radiotherapy on the immune landscape in oesophageal adenocarcinoma
Noel E Donlon, Maria Davern, Fiona O’Connell, Andrew Sheppard, Aisling Heeran, Anshul Bhardwaj, Christine Butler, Ravi Narayanasamy, Claire Donohoe, James J Phelan, Niamh Lynam-Lennon, Margaret R Dunne, Stephen Maher, Jacintha O’Sullivan, John V Reynolds, Joanne Lysaght
Noel E Donlon, Maria Davern, Fiona O’Connell, Andrew Sheppard, Aisling Heeran, Anshul Bhardwaj, Christine Butler, Ravi Narayanasamy, Claire Donohoe, James J Phelan, Niamh Lynam-Lennon, Margaret R Dunne, Stephen Maher, Jacintha O’Sullivan, John V Reynolds, Joanne Lysaght, Department of Surgery, Trinity Translational Medicine Institute, St James Hospital, Dublin D08, Ireland
Author contributions: Donlon NE and Davern M contributed equally to this work; Donlon NE and Davern M contributed to experimental design and execution, and manuscript drafting and revision; O’Connell F and Sheppard A contributed to experiments; Heeran A, Bhardwaj A, and Butler C contributed to sample acquisition; Narayanasamy R, Donohoe C, Phelan JJ, Lynam-Lennon N, Dunne MR, and Maher S contributed to concept design; Phelan JJ contributed to statistical analysis; O’Sullivan J, Reynolds JV, and Lysaght J contributed to paper revision and supervision of the project.
Institutional review board statement: The study was reviewed and approved by the Tallaght/St James’s Hospital Ethics Committee.
Conflict-of-interest statement: There are no conflicts of interest to report.
Data sharing statement: Data generated in this study will be available upon specific request from the corresponding author.
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, Assistant Professor, Department of Surgery, Trinity Translational Medicine Institute, St James Hospital, James’s Street, Dublin D08, Ireland. donlonn@tcd.ie
Received: December 3, 2021 Peer-review started: December 3, 2021 First decision: January 27, 2022 Revised: February 19, 2022 Accepted: April 26, 2022 Article in press: April 26, 2022 Published online: June 7, 2022
ARTICLE HIGHLIGHTS
Research background
Oesophageal cancer is represents a difficult treatment dilemma with poor 5 year overall survival due to presentation at advanced stages due to its indolent nature as well as poor treatment responses to conventional therapies.
Research motivation
The advent of immunotherapy represents a shift in the multimodal treatment paradigm for esophageal cancer and has had mixed results in many solid tumours to date. The Checkmate 577 trial is a landmark study and is sure to revolutionize immune checkpoint blockade as the treatment modality of choice in the adjuvant setting.
Research objectives
To determine the impact of radiotherapy (RT) on immune checkpoint expression, and to determine the prevailing immune milieu in terms of markers of angiogenesis, cytokines and metastatic markers.
Research methods
This hybrid in vitro and ex vivo study is a mixture of flow cytometry, enzyme-linked immunosorbent assay kit work and cell viability by a cell counting kit-8 assay.
Research results
Radiation results in a decrease in angiogenic and metastatic markers with an increase in anti-tumour cytokines. There were two distinct subpopulations, with one cohort of patients demonstrating increased checkpoint expression as a consequence of radiation and a separate cohort demonstrating the opposite effects. The cohort with increased checkpoint expression had poorer treatment responses and were associated with adverse tumour biology.
Research conclusions
Oesophageal cancer represents an immune active tumour and is a viable target in both the neoadjuvant and adjuvant setting and should be combined with RT to exert maximum synergistic effects.
Research perspectives
This seminal study is the first of its kind and is a truly clinical and translational evaluation of the immune landscape of esophageal cancer.
