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

Author:

McGranahan Nicholas123,Furness Andrew J. S.34,Rosenthal Rachel3,Ramskov Sofie5,Lyngaa Rikke5,Saini Sunil Kumar5,Jamal-Hanjani Mariam3,Wilson Gareth A.13,Birkbak Nicolai J.13,Hiley Crispin T.13,Watkins Thomas B. K.13,Shafi Seema3,Murugaesu Nirupa3,Mitter Richard1,Akarca Ayse U.46,Linares Joseph46,Marafioti Teresa46,Henry Jake Y.34,Van Allen Eliezer M.789,Miao Diana78,Schilling Bastian1011,Schadendorf Dirk1011,Garraway Levi A.789,Makarov Vladimir12,Rizvi Naiyer A.13,Snyder Alexandra1415,Hellmann Matthew D.1415,Merghoub Taha1416,Wolchok Jedd D.141516,Shukla Sachet A.78,Wu Catherine J.781718,Peggs Karl S.34,Chan Timothy A.12,Hadrup Sine R.5,Quezada Sergio A.34,Swanton Charles13

Affiliation:

1. The Francis Crick Institute, London WC2A 3LY, UK.

2. Centre for Mathematics and Physics in the Life Sciences and Experimental Biology (CoMPLEX), University College London (UCL), London WC1E 6BT, UK.

3. Cancer Research UK Lung Cancer Centre of Excellence, UCL Cancer Institute, London WC1E 6BT, UK.

4. Cancer Immunology Unit, UCL Cancer Institute, UCL, London WC1E 6BT, UK.

5. Section for Immunology and Vaccinology, National Veterinary Institute, Technical University of Denmark, 1970 Frederiksberg C, Denmark.

6. Department of Cellular Pathology, UCL, London WC1E 6BT, UK.

7. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.

8. Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

9. Center for Cancer Precision Medicine, Dana-Farber Cancer Institute, Boston, MA 02215, USA.

10. Department of Dermatology, University Hospital, University Duisburg–Essen, 45147 Essen, Germany.

11. German Cancer Consortium (DKTK), 69121 Heidelberg, Germany.

12. Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

13. Hematology/Oncology Division, 177 Fort Washington Avenue, Columbia University, New York, NY 10032, USA.

14. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

15. Weill Cornell Medical College, New York, NY 10065, USA.

16. Ludwig Collaborative Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

17. Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.

18. Department of Internal Medicine, Brigham and Woman’s Hospital, Boston, MA 02115, USA.

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

Funder

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

NIH/National Cancer Institute

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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