Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade
The Francis Crick Institute · CRUK Lung Cancer Centre of Excellence · +15 more institutions
Abstract
As tumors grow, they acquire mutations, some of which create neoantigens that influence the response of patients to immune checkpoint inhibitors. We explored the impact of neoantigen intratumor heterogeneity (ITH) on antitumor immunity. Through integrated analysis of ITH and neoantigen burden, we demonstrate a relationship between clonal neoantigen burden and overall survival in primary lung adenocarcinomas. CD8(+)tumor-infiltrating lymphocytes reactive to clonal neoantigens were identified in early-stage non-small cell lung cancer and expressed high levels of PD-1. Sensitivity to PD-1 and CTLA-4 blockade in patients with advanced NSCLC and melanoma was enhanced in tumors enriched for clonal neoantigens. T…
Citation impact
- FWCI
- 171.83
- Percentile
- 100%
- References
- 39
Authors
36- NMNicholas McGranahanCorresponding
The Francis Crick Institute, CRUK Lung Cancer Centre of Excellence, University College London
- AJAndrew J.S. FurnessCorresponding
Cancer Research UK, CRUK Lung Cancer Centre of Excellence, University College London
- RRRachel RosenthalCorresponding
CRUK Lung Cancer Centre of Excellence, University College London
- SRSofie Ramskov
Technical University of Denmark
- RLRikke Lyngaa
Technical University of Denmark
Topics & keywords
- Blockade
- Immune checkpoint
- Immune system
- Immunology
- Antibody
- Biology
- Immunotherapy
- Receptor
- No poverty
Funding
- PCProstate Cancer Foundation
- BCBreast Cancer Research Foundation
- LALeukemia and Lymphoma Society
- BFBlavatnik Family Foundation
- CRCancer Research UK
- NNNovo Nordisk UK Research Foundation
- RTRosetrees Trust
- SFSeventh Framework Programme
- NHNational Heart, Lung, and Blood InstituteAward: 1R01CA155010-02
- NCNational Cancer InstituteAwards: 1R01CA184922-01, 1R01CA182461-01
- HEH2020 European Research Council