Cited by 2,144Cancer Cells and MetastasisEffects of Radiation ExposureCancer, Hypoxia, and Metabolism

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The tumour microenvironment after radiotherapy: mechanisms of resistance and recurrence

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Barker, Holly E., Paget, James T. E., Khan, Aadil A., Harrington, Kevin J.·2015·Nature Reviews Cancer

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Abstract

Radiotherapy plays a central part in curing cancer. For decades, most research on improving treatment outcomes has focused on modulating radiation-induced biological effects on cancer cells. Recently, we have better understood that components within the tumour microenvironment have pivotal roles in determining treatment outcomes. In this Review, we describe vascular, stromal and immunological changes that are induced in the tumour microenvironment by irradiation and discuss how these changes may promote radioresistance and tumour recurrence. We also highlight how this knowledge is guiding the development of new treatment paradigms in which biologically targeted agents will be combined with radiotherapy.

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“proposed various immunological mechanisms for radiosensitization, including: (a) increasing the number and activation levels of dendritic cells, (b) effective T-cell recruitment and activation, (c) inhibition of T-cell exhaustion and abrogation of inhibitory signaling, and (d) induction of specific cytokine (GM-CSF, I…”
Background

Authors: Barker, H. E., Paget, J. T. E., Khan, A. A., & Harrington, K. J.
Affiliations: Institute of Cancer Research (GB)
Corresponding author: Barker, Holly E.
ORCID: Barker, Holly E.
Paget, James T. E.
Khan, Aadil A.
Harrington, Kevin J.
Venue: Nature Reviews Cancer
Publisher: Springer Science and Business Media LLC
Published: 2015-06-24
Volume: 15
Issue: 7
Pages: 409-425
ISSN: 1474-175X (ISSN-L)
1474-1768
DOI: 10.1038/nrc3958
PMC: PMC4896389
OpenAlex: W1912124796
Cited by: 2,144
References: 200
Citations by year: 2026: 181 · 2025: 215 · 2024: 246 · 2023: 242 · 2022: 249 · 2021: 256 · 2020: 230 · 2019: 175 · 2018: 161 · 2017: 119 · 2016: 63 · 2015: 7
FWCI: 12.40
Type: journal article
Language: en
Update notices: erratum (2015-07-24)
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Nature reviews. Cancer (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: Cancer Research UK (C46 ⁄ A10588, C7224/A13407, A13407, 13407)
National Institute for Health and Care Research (CL-2014-22-003)
Rosetrees Trust
Topics: Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Keywords: tumor microenvironment, radioresistance (biology), radiotherapy, tumor stroma, tumor recurrence, vascular changes, immunological changes, combination therapy, molecularly targeted agents
MeSH terms: Animals, Fibroblasts, Humans, Immune Tolerance, Neoplasm Recurrence, Local, Neoplasms, Radiation Tolerance, Cell Hypoxia, Transforming Growth Factor beta, Vascular Endothelial Growth Factor A, Tumor Microenvironment

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The tumour microenvironment after radiotherapy: mechanisms of resistance and recurrence

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