Key Parameters of Tumor Epitope Immunogenicity Revealed Through a Consortium Approach Improve Neoantigen Prediction

Daniel K Wells; Marit M van Buuren; Kristen K Dang; Vanessa M Hubbard-Lucey; Kathleen C F Sheehan; Katie M Campbell; Andrew Lamb; Jeffrey P Ward; John Sidney; Ana B Blazquez; Andrew J Rech; Jesse M Zaretsky; Begonya Comin-Anduix; Alphonsus H C Ng; William Chour; Thomas V Yu; Hira Rizvi; Jia M Chen; Patrice Manning; Gabriela M Steiner; Xengie C Doan; Tumor Neoantigen Selection Alliance; Taha Merghoub; Justin Guinney; Adam Kolom; Cheryl Selinsky; Antoni Ribas; Matthew D Hellmann; Nir Hacohen; Alessandro Sette; James R Heath; Nina Bhardwaj; Fred Ramsdell; Robert D Schreiber; Ton N Schumacher; Pia Kvistborg; Nadine A Defranoux

doi:10.1016/j.cell.2020.09.015

Key Parameters of Tumor Epitope Immunogenicity Revealed Through a Consortium Approach Improve Neoantigen Prediction

Cell. 2020 Oct 29;183(3):818-834.e13. doi: 10.1016/j.cell.2020.09.015. Epub 2020 Oct 9.

Authors

Daniel K Wells¹, Marit M van Buuren², Kristen K Dang³, Vanessa M Hubbard-Lucey⁴, Kathleen C F Sheehan⁵, Katie M Campbell⁶, Andrew Lamb³, Jeffrey P Ward⁷, John Sidney⁸, Ana B Blazquez⁹, Andrew J Rech¹⁰, Jesse M Zaretsky⁶, Begonya Comin-Anduix¹¹, Alphonsus H C Ng¹², William Chour¹³, Thomas V Yu³, Hira Rizvi¹⁴, Jia M Chen⁶, Patrice Manning¹⁵, Gabriela M Steiner¹⁵, Xengie C Doan³; Tumor Neoantigen Selection Alliance; Taha Merghoub¹⁶, Justin Guinney¹⁷, Adam Kolom¹⁸, Cheryl Selinsky¹⁵, Antoni Ribas¹⁹, Matthew D Hellmann²⁰, Nir Hacohen²¹, Alessandro Sette²², James R Heath²³, Nina Bhardwaj²⁴, Fred Ramsdell¹⁵, Robert D Schreiber²⁵, Ton N Schumacher²⁶, Pia Kvistborg²⁷, Nadine A Defranoux²⁸

Collaborators

Tumor Neoantigen Selection Alliance:
Aly A Khan, Amit Lugade, Ana M Mijalkovic Lazic, Angela A Elizabeth Frentzen, Arbel D Tadmor, Ariella S Sasson, Arjun A Rao, Baikang Pei, Barbara Schrörs, Beata Berent-Maoz, Beatriz M Carreno, Bin Song, Bjoern Peters, Bo Li, Brandon W Higgs, Brian J Stevenson, Christian Iseli, Christopher A Miller, Christopher A Morehouse, Cornelis J M Melief, Cristina Puig-Saus, Daphne van Beek, David Balli, David Gfeller, David Haussler, Dirk Jäger, Eduardo Cortes, Ekaterina Esaulova, Elham Sherafat, Francisco Arcila, Gabor Bartha, Geng Liu, George Coukos, Guilhem Richard, Han Chang, Han Si, Inka Zörnig, Ioannis Xenarios, Ion Mandoiu, Irsan Kooi, James P Conway, Jan H Kessler, Jason A Greenbaum, Jason F Perera, Jason Harris, Jasreet Hundal, Jennifer M Shelton, Jianmin Wang, Jiaqian Wang, Joel Greshock, Jonathon Blake, Joseph Szustakowski, Julia Kodysh, Juliet Forman, Lei Wei, Leo J Lee, Lorenzo F Fanchi, Maarten Slagter, Maren Lang, Markus Mueller, Martin Lower, Mathias Vormehr, Maxim N Artyomov, Michael Kuziora, Michael Princiotta, Michal Bassani-Sternberg, Mignonette Macabali, Milica R Kojicic, Naibo Yang, Nevena M Ilic Raicevic, Nicolas Guex, Nicolas Robine, Niels Halama, Nikola M Skundric, Ognjen S Milicevic, Pascal Gellert, Patrick Jongeneel, Pornpimol Charoentong, Pramod K Srivastava, Prateek Tanden, Priyanka Shah, Qiang Hu, Ravi Gupta, Richard Chen, Robert Petit, Robert Ziman, Rolf Hilker, Sachet A Shukla, Sahar Al Seesi, Sean M Boyle, Si Qiu, Siranush Sarkizova, Sofie Salama, Song Liu, Song Wu, Sriram Sridhar, Steven L C Ketelaars, Suchit Jhunjhunwala, Tatiana Shcheglova, Thierry Schuepbach, Todd H Creasy, Veliborka Josipovic, Vladimir B Kovacevic, Weixuan Fu, Willem-Jan Krebber, Yi-Hsiang Hsu, Yinong Sebastian, Zeynep Kosaloglu- Yalcin, Zhiqin Huang

Affiliations

¹ Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA. Electronic address: dwells@parkerici.org.
² Division of Molecular Oncology and Immunology, the Netherlands Cancer Institute, Amsterdam, the Netherlands; T Cell Immunology, Biopharmaceutical New Technologies (BioNTech) Corporation, BioNTech US, Cambridge, MA, USA.
³ Computational Oncology, Sage Bionetworks, Seattle, WA, USA.
⁴ Anna-Maria Kellen Clinical Accelerator, Cancer Research Institute, New York, NY, USA.
⁵ Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, St. Louis, MO, USA; The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO, USA.
⁶ Division of Hematology and Oncology, Department of Medicine, Johnson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
⁷ Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
⁸ Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
⁹ Division of Hematology and Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
¹⁰ Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA; Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
¹¹ Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA; Department of Surgery, David Geffen School of Medicine, Johnson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA, USA.
¹² Institute for Systems Biology, Seattle, WA, USA.
¹³ Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
¹⁴ Druckenmiller Center for Lung Cancer Research, MSKCC, New York, NY, USA.
¹⁵ Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA.
¹⁶ Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA; Department of Medicine, MSKCC, New York, NY, USA; Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
¹⁷ Computational Oncology, Sage Bionetworks, Seattle, WA, USA; Biomedical Informatics and Medical Education, University of Washington, Seattle, WA, USA.
¹⁸ Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA; Anna-Maria Kellen Clinical Accelerator, Cancer Research Institute, New York, NY, USA.
¹⁹ Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA; Division of Hematology and Oncology, Department of Medicine, Johnson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA; Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
²⁰ Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA; Druckenmiller Center for Lung Cancer Research, MSKCC, New York, NY, USA; Department of Medicine, MSKCC, New York, NY, USA; Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
²¹ Broad Institute of MIT and Harvard, Cambridge, MA, USA; Massachusetts General Hospital Cancer Center, Boston, MA, USA.
²² Division of Hematology and Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
²³ Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA; Institute for Systems Biology, Seattle, WA, USA.
²⁴ Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA; Division of Hematology and Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
²⁵ Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, St. Louis, MO, USA; The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO, USA.
²⁶ Division of Molecular Oncology and Immunology, Oncode Institute, the Netherlands Cancer Institute, Amsterdam, the Netherlands.
²⁷ Division of Molecular Oncology and Immunology, the Netherlands Cancer Institute, Amsterdam, the Netherlands.
²⁸ Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA. Electronic address: ndefranoux@parkerici.org.

Abstract

Many approaches to identify therapeutically relevant neoantigens couple tumor sequencing with bioinformatic algorithms and inferred rules of tumor epitope immunogenicity. However, there are no reference data to compare these approaches, and the parameters governing tumor epitope immunogenicity remain unclear. Here, we assembled a global consortium wherein each participant predicted immunogenic epitopes from shared tumor sequencing data. 608 epitopes were subsequently assessed for T cell binding in patient-matched samples. By integrating peptide features associated with presentation and recognition, we developed a model of tumor epitope immunogenicity that filtered out 98% of non-immunogenic peptides with a precision above 0.70. Pipelines prioritizing model features had superior performance, and pipeline alterations leveraging them improved prediction performance. These findings were validated in an independent cohort of 310 epitopes prioritized from tumor sequencing data and assessed for T cell binding. This data resource enables identification of parameters underlying effective anti-tumor immunity and is available to the research community.

Keywords: TESLA; epitope; immunogenicity; immunogenomics; immunotherapy; neoantigen.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Alleles
Antigen Presentation / immunology
Antigens, Neoplasm / immunology*
Cohort Studies
Epitopes / immunology*
Humans
Neoplasms / immunology*
Peptides / immunology
Programmed Cell Death 1 Receptor
Reproducibility of Results

Substances

Antigens, Neoplasm
Epitopes
Peptides
Programmed Cell Death 1 Receptor

Abstract

Publication types

MeSH terms

Substances

Grants and funding