Epitope spreading toward wild-type melanocyte-lineage antigens rescues suboptimal immune checkpoint blockade responses

Author:

Lo Jennifer A.12ORCID,Kawakubo Masayoshi1,Juneja Vikram R.34,Su Mack Y.12,Erlich Tal H.12ORCID,LaFleur Martin W.345ORCID,Kemeny Lajos V.12ORCID,Rashid Mamunur6ORCID,Malehmir Mohsen7ORCID,Rabi S. Alireza7,Raghavan Rumya89,Allouche Jennifer12ORCID,Kasumova Gyulnara7,Frederick Dennie T.7,Pauken Kristen E.34ORCID,Weng Qing Yu12ORCID,Pereira da Silva Marcelo1ORCID,Xu Yu10,van der Sande Anita A. J.12,Silkworth Whitney12ORCID,Roider Elisabeth12111213,Browne Edward P.14ORCID,Lieb David J.8ORCID,Wang Belinda815ORCID,Garraway Levi A.815,Wu Catherine J.815ORCID,Flaherty Keith T.2ORCID,Brinckerhoff Constance E.16,Mullins David W.17,Adams David J.6,Hacohen Nir28ORCID,Hoang Mai P.18ORCID,Boland Genevieve M.7ORCID,Freeman Gordon J.1519ORCID,Sharpe Arlene H.348ORCID,Manstein Dieter1ORCID,Fisher David E.12ORCID

Affiliation:

1. Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.

2. Massachusetts General Hospital Cancer Center, Boston, MA 02114, USA.

3. Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.

4. Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women’s Hospital, Boston, MA 02115, USA.

5. Division of Medical Sciences, Harvard Medical School, Boston, MA 02115, USA.

6. Experimental Cancer Genetics, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1HH, UK.

7. Division of Surgical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.

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

9. Harvard-MIT Health Sciences and Technology Program, Cambridge, MA 02139, USA.

10. Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.

11. Department of Dermatology and Allergology, University of Szeged, Szeged 6727, Hungary.

12. Department of Dermatology, Venerology, and Allergology, Kantonsspital St. Gallen, St. Gallen 9000, Switzerland.

13. University of Zurich, Zurich 8006, Switzerland.

14. Department of Medicine, UNC-Chapel Hill, Chapel Hill, NC 27599, USA.

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

16. Departments of Medicine and Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA.

17. Departments of Medical Education and Microbiology/Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA.

18. Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.

19. Harvard Medical School, Boston, MA 02115, USA.

Abstract

Neoantigens sensitize melanomas to checkpoint blockade and trigger epitope spreading to self-antigens, a process mimicked by combination immunotherapy.

Funder

National Science Foundation

National Institutes of Health

National Cancer Institute

Cancer Research Institute

Leukemia and Lymphoma Society

Dr. Miriam and Sheldon G. Adelson Medical Research Foundation

Cancer Research UK

Swiss National Science Foundation

Dr. Mildred Scheel Stiftung für Krebsforschung

Publisher

American Association for the Advancement of Science (AAAS)

Subject

General Medicine

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