Cited by 3,065Cancer Immunotherapy and BiomarkersImmunotherapy and Immune ResponsesCancer Genomics and Diagnostics

Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade

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McGranahan, Nicholas, Furness, Andrew J. S., Rosenthal, Rachel, Ramskov, Sofie, Lyngaa, Rikke, Saini, Sunil Kumar, Jamal-Hanjani, Mariam, Wilson, Gareth A. +28 more·2016·Science

Abstract

The cellular ancestry of tumor antigens: One contributing factor in antitumor immunity is the repertoire of neoantigens created by genetic mutations within tumor cells. Like the corresponding mutations, these neoantigens show intratumoral heterogeneity. Some are present in all tumor cells (clonal), and others are present in only a fraction of cells (subclonal). In a study of lung cancer and melanoma, McGranahan et al. found that a high burden of clonal tumor neoantigens correlated with improved patient survival, an increased presence of tumor-infiltrating lymphocytes, and a durable response to immunotherapy. Science , this issue p. 1463

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  1. [18]Alexandrov LB Nature 500 415 421 2013 23945592 PMC3776390

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Authors
McGranahan, N., Furness, A. J. S., Rosenthal, R., Ramskov, S., Lyngaa, R., Saini, S. K., Jamal-Hanjani, M., Wilson, G. A., Birkbak, N. J., Hiley, C. T., Watkins, T. B. K., Shafi, S., Murugaesu, N., Mitter, R., Akarca, A. U., Linares, J., Marafioti, T., Henry, J. Y., Van Allen, E. M., Miao, D., Schilling, B., Schadendorf, D., Garraway, L. A., Makarov, V., Rizvi, N. A., Snyder, A., Hellmann, M. D., Merghoub, T., Wolchok, J. D., Shukla, S. A., Wu, C. J., Peggs, K. S., Chan, T. A., Hadrup, S. R., Quezada, S. A., & Swanton, C.
Affiliations
  • The Francis Crick Institute (GB)
  • Cancer Research UK (GB)
  • Technical University of Denmark (DK)
  • Cancer Research UK Lung Cancer Centre of Excellence, UCL Cancer Institute, London WC1E 6BT, UK.
  • University College London (GB)
  • Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Broad Institute (US)
  • Deutsches Konsortium für Translationale Krebsforschung (DE)
  • Memorial Sloan Kettering Cancer Center (US)
  • Columbia University Irving Medical Center (US)
Corresponding author
  • McGranahan, Nicholas
  • Furness, Andrew J. S.
  • Rosenthal, Rachel
  • Quezada, Sergio A.
  • Swanton, Charles
Venue
Science
Published
2016-03-25
Volume
351
Issue
6280
Pages
1463-1469
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W2291298003
Cited by
3,065
References
38
Citations by year
2026: 163 · 2025: 192 · 2024: 257 · 2023: 270 · 2022: 312 · 2021: 412 · 2020: 372 · 2019: 366 · 2018: 298 · 2017: 278 · 2016: 141 · 2015: 1 · 2014: 1
FWCI
194.42
Type
journal article
Language
en
Open access
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • Figshare (submittedVersion, cc-by)
  • Technical University of Denmark, DTU Orbit (Technical University of Denmark, DTU) (submittedVersion, other-oa)
Funders
  • Cancer Research UK (CRUK)
  • Rosetrees Trust
  • NovoNordisk Foundation
  • Prostate Cancer Foundation
  • Breast Cancer Research Foundation
  • European Research Council
  • EU FP7
  • Sam Keen Foundation
  • Leukemia and Lymphoma Society
  • Blavatnik Family Foundation
  • NIH/National Heart, Lung, and Blood Institute (1R01CA155010-02)
  • NIH/National Cancer Institute (1R01CA182461-01, 1R01CA184922-01)
Topics
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
Keywords
intratumoral heterogeneity, immune checkpoint blockade, anti-PD-1 therapy, CTLA-4 blockade, CD8+ T cells, tumor-infiltrating lymphocytes, lung adenocarcinoma, non-small cell lung cancer, melanoma, mutational burden, antitumor immunity, overall survival, immune checkpoint inhibitor response
MeSH terms
Adenocarcinoma of Lung, Adenocarcinoma, Aged, Aged, 80 and over, Antigens, Neoplasm, Antineoplastic Agents, Carcinoma, Non-Small-Cell Lung, Female, Humans, Immunologic Surveillance, Lung Neoplasms, Male, Melanoma, Middle Aged, Mutation, Skin Neoplasms, CD4-Positive T-Lymphocytes, Lymphocytes, Tumor-Infiltrating, Cell Cycle Checkpoints, CTLA-4 Antigen, Programmed Cell Death 1 Receptor

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