4.6 Article

Impact of cancer evolution on immune surveillance and checkpoint inhibitor response

Journal

SEMINARS IN CANCER BIOLOGY
Volume 84, Issue -, Pages 89-102

Publisher

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

  1. National Institute for Health Research (NIHR) Academic Clinical Lecturer fellowship
  2. Academy of Medical Sciences
  3. Cancer Research UK
  4. NIHR Biomedical Research Centre (BRC) at University College London Hospitals
  5. NIHR BRC at University College London Hospitals
  6. ideas 2 innovation (i2i) translation scheme at the Francis Crick Institute
  7. Breast Cancer Research Foundation (BCRF)
  8. Francis Crick Institute - Cancer Research UK
  9. UK Medical Research Council
  10. Wellcome Trust
  11. Cancer Research UK (TRAC-ERx, PEACE and CRUK Cancer Immunotherapy Catalyst Network)
  12. CRUK Lung Cancer Centre of Excellence
  13. Rosetrees Trust
  14. Novo-Nordisk Foundation
  15. Stand Up To Cancer-LUNGevity-American Lung Association Lung Cancer Interception Dream Team Translational Research Grant
  16. Stand Up To Cancer is a programme of the Entertainment Industry Foundation
  17. European Research Council (ERC) under the European Union's Seventh Frame-work Programme (FP7/2007-2013)
  18. European Commission
  19. ERC Advanced Grant (PROTEUS) from the European Research Council under the European Union
  20. European Union's Horizon 2020 research and innovation programme
  21. [FC001169]
  22. [FC001202]
  23. [ID16584]
  24. [SU2C-AACR-DT23-17]
  25. [FP7-THESEUS-617844]
  26. [607722]
  27. [835297]
  28. [665233]

Ask authors/readers for more resources

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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