Journal
SEMINARS IN CANCER BIOLOGY
Volume 84, Issue -, Pages 89-102Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.semcancer.2021.02.013
Keywords
Intratumour heterogeneity; Neoantigens; Genomic instability; Immune surveillance; Immune checkpoint inhibitors
Categories
Funding
- National Institute for Health Research (NIHR) Academic Clinical Lecturer fellowship
- Academy of Medical Sciences
- Cancer Research UK
- NIHR Biomedical Research Centre (BRC) at University College London Hospitals
- NIHR BRC at University College London Hospitals
- ideas 2 innovation (i2i) translation scheme at the Francis Crick Institute
- Breast Cancer Research Foundation (BCRF)
- Francis Crick Institute - Cancer Research UK
- UK Medical Research Council
- Wellcome Trust
- Cancer Research UK (TRAC-ERx, PEACE and CRUK Cancer Immunotherapy Catalyst Network)
- CRUK Lung Cancer Centre of Excellence
- Rosetrees Trust
- Novo-Nordisk Foundation
- Stand Up To Cancer-LUNGevity-American Lung Association Lung Cancer Interception Dream Team Translational Research Grant
- Stand Up To Cancer is a programme of the Entertainment Industry Foundation
- European Research Council (ERC) under the European Union's Seventh Frame-work Programme (FP7/2007-2013)
- European Commission
- ERC Advanced Grant (PROTEUS) from the European Research Council under the European Union
- European Union's Horizon 2020 research and innovation programme
- [FC001169]
- [FC001202]
- [ID16584]
- [SU2C-AACR-DT23-17]
- [FP7-THESEUS-617844]
- [607722]
- [835297]
- [665233]
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Intratumour heterogeneity (ITH) can affect the response of patients to immune checkpoint inhibitor (CPI) therapy, confounding the accuracy of predictive biomarkers and playing a role in both immune surveillance and immune evasion. A deeper understanding of the interaction between ITH and the immune system can potentially increase the proportion of patients experiencing durable responses from CPI therapy.
Intratumour heterogeneity (ITH) is pervasive across all cancers studied and may provide the evolving tumour multiple routes to escape immune surveillance. Immune checkpoint inhibitors (CPIs) are rapidly becoming standard of care for many cancers. Here, we discuss recent work investigating the influence of ITH on patient response to immune checkpoint inhibitor (CPI) therapy. At its simplest, ITH may confound the diagnostic ac-curacy of predictive biomarkers used to stratify patients for CPI therapy. Furthermore, ITH is fuelled by mechanisms of genetic instability that can both engage immune surveillance and drive immune evasion. A greater appreciation of the interplay between ITH and the immune system may hold the key to increasing the proportion of patients experiencing durable responses from CPI therapy.
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