Cargando…

Radiation and Immunotherapy in Upper Gastrointestinal Cancers: The Current State of Play

Radiotherapy remains one of the contemporary cornerstones of cancer treatment in the neoadjuvant, curative, adjuvant and palliative settings, either in isolation or as a multimodal approach. Moreover, recent advances in targeted immune checkpoint therapy have firmly established immunotherapy as the...

Descripción completa

Detalles Bibliográficos
Autores principales: Donlon, Noel E., Power, Robert, Hayes, Conall, Davern, Maria, Reynolds, John V., Lysaght, Joanne
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865314/
https://www.ncbi.nlm.nih.gov/pubmed/33499003
http://dx.doi.org/10.3390/ijms22031071
_version_ 1783647817227567104
author Donlon, Noel E.
Power, Robert
Hayes, Conall
Davern, Maria
Reynolds, John V.
Lysaght, Joanne
author_facet Donlon, Noel E.
Power, Robert
Hayes, Conall
Davern, Maria
Reynolds, John V.
Lysaght, Joanne
author_sort Donlon, Noel E.
collection PubMed
description Radiotherapy remains one of the contemporary cornerstones of cancer treatment in the neoadjuvant, curative, adjuvant and palliative settings, either in isolation or as a multimodal approach. Moreover, recent advances in targeted immune checkpoint therapy have firmly established immunotherapy as the fourth pillar in cancer therapy alongside surgery, chemotherapy and notably radiotherapy. There is emerging evidence to suggest both radioresistance and reduced efficacy of immune checkpoint blockade (ICB) are potentiated by the tumour microenvironment (TME) and in fact modulating aspects of this immunosuppressive milieu is instrumental to unlocking anti-tumour immunity. The response rates of Upper Gastrointestinal (UGI) malignancies to ICB remains modest at 10–15%, compared to melanoma at 20–40%. Harnessing the effects of radiotherapy through remodelling of the TME using ICB as a radiosensitisor is an avenue showing promise. Here we explore the rationale behind combining radiotherapy with ICB, as a symbiotic relationship in shifting the balance in favour of anti-tumour immunity. We discuss the effects of radiotherapy on immunogenic cell death, the concept of the abscopal effect, the importance of the cGAS STING pathway, and their relevance in the context of the tumour microenvironment. Furthermore, dosing and timing of radiotherapy and ICB is now being evaluated for its synergistic effects on host tumour immunity, and we review the ongoing efforts and current available literature for single agent and dual agent ICB in combination multimodal therapy for both locally advanced operable and metastatic disease of the upper gastrointestinal tract.
format Online
Article
Text
id pubmed-7865314
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-78653142021-02-07 Radiation and Immunotherapy in Upper Gastrointestinal Cancers: The Current State of Play Donlon, Noel E. Power, Robert Hayes, Conall Davern, Maria Reynolds, John V. Lysaght, Joanne Int J Mol Sci Review Radiotherapy remains one of the contemporary cornerstones of cancer treatment in the neoadjuvant, curative, adjuvant and palliative settings, either in isolation or as a multimodal approach. Moreover, recent advances in targeted immune checkpoint therapy have firmly established immunotherapy as the fourth pillar in cancer therapy alongside surgery, chemotherapy and notably radiotherapy. There is emerging evidence to suggest both radioresistance and reduced efficacy of immune checkpoint blockade (ICB) are potentiated by the tumour microenvironment (TME) and in fact modulating aspects of this immunosuppressive milieu is instrumental to unlocking anti-tumour immunity. The response rates of Upper Gastrointestinal (UGI) malignancies to ICB remains modest at 10–15%, compared to melanoma at 20–40%. Harnessing the effects of radiotherapy through remodelling of the TME using ICB as a radiosensitisor is an avenue showing promise. Here we explore the rationale behind combining radiotherapy with ICB, as a symbiotic relationship in shifting the balance in favour of anti-tumour immunity. We discuss the effects of radiotherapy on immunogenic cell death, the concept of the abscopal effect, the importance of the cGAS STING pathway, and their relevance in the context of the tumour microenvironment. Furthermore, dosing and timing of radiotherapy and ICB is now being evaluated for its synergistic effects on host tumour immunity, and we review the ongoing efforts and current available literature for single agent and dual agent ICB in combination multimodal therapy for both locally advanced operable and metastatic disease of the upper gastrointestinal tract. MDPI 2021-01-22 /pmc/articles/PMC7865314/ /pubmed/33499003 http://dx.doi.org/10.3390/ijms22031071 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Donlon, Noel E.
Power, Robert
Hayes, Conall
Davern, Maria
Reynolds, John V.
Lysaght, Joanne
Radiation and Immunotherapy in Upper Gastrointestinal Cancers: The Current State of Play
title Radiation and Immunotherapy in Upper Gastrointestinal Cancers: The Current State of Play
title_full Radiation and Immunotherapy in Upper Gastrointestinal Cancers: The Current State of Play
title_fullStr Radiation and Immunotherapy in Upper Gastrointestinal Cancers: The Current State of Play
title_full_unstemmed Radiation and Immunotherapy in Upper Gastrointestinal Cancers: The Current State of Play
title_short Radiation and Immunotherapy in Upper Gastrointestinal Cancers: The Current State of Play
title_sort radiation and immunotherapy in upper gastrointestinal cancers: the current state of play
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865314/
https://www.ncbi.nlm.nih.gov/pubmed/33499003
http://dx.doi.org/10.3390/ijms22031071
work_keys_str_mv AT donlonnoele radiationandimmunotherapyinuppergastrointestinalcancersthecurrentstateofplay
AT powerrobert radiationandimmunotherapyinuppergastrointestinalcancersthecurrentstateofplay
AT hayesconall radiationandimmunotherapyinuppergastrointestinalcancersthecurrentstateofplay
AT davernmaria radiationandimmunotherapyinuppergastrointestinalcancersthecurrentstateofplay
AT reynoldsjohnv radiationandimmunotherapyinuppergastrointestinalcancersthecurrentstateofplay
AT lysaghtjoanne radiationandimmunotherapyinuppergastrointestinalcancersthecurrentstateofplay