IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v606y2022i7913d10.1038_s41586-022-04735-9.html
   My bibliography  Save this article

Neoantigen quality predicts immunoediting in survivors of pancreatic cancer

Author

Listed:
  • Marta Łuksza

    (Icahn School of Medicine at Mount Sinai)

  • Zachary M. Sethna

    (Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center)

  • Luis A. Rojas

    (Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center)

  • Jayon Lihm

    (Memorial Sloan Kettering Cancer Center)

  • Barbara Bravi

    (Université PSL, CNRS, Sorbonne Université, Université de Paris
    Imperial College London)

  • Yuval Elhanati

    (Memorial Sloan Kettering Cancer Center)

  • Kevin Soares

    (Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center)

  • Masataka Amisaki

    (Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center)

  • Anton Dobrin

    (Memorial Sloan Kettering Cancer Center
    Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center)

  • David Hoyos

    (Memorial Sloan Kettering Cancer Center)

  • Pablo Guasp

    (Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center)

  • Abderezak Zebboudj

    (Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center)

  • Rebecca Yu

    (Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center)

  • Adrienne Kaya Chandra

    (Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center)

  • Theresa Waters

    (Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center)

  • Zagaa Odgerel

    (Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center)

  • Joanne Leung

    (Memorial Sloan Kettering Cancer Center)

  • Rajya Kappagantula

    (Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center)

  • Alvin Makohon-Moore

    (Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center)

  • Amber Johns

    (Garvan Institute of Medical Research)

  • Anthony Gill

    (Garvan Institute of Medical Research
    University of Sydney)

  • Mathieu Gigoux

    (Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center)

  • Jedd Wolchok

    (Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center)

  • Taha Merghoub

    (Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center)

  • Michel Sadelain

    (Memorial Sloan Kettering Cancer Center
    Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center)

  • Erin Patterson

    (Memorial Sloan Kettering Cancer Center)

  • Remi Monasson

    (Université PSL, CNRS, Sorbonne Université, Université de Paris)

  • Thierry Mora

    (Université PSL, CNRS, Sorbonne Université, Université de Paris)

  • Aleksandra M. Walczak

    (Université PSL, CNRS, Sorbonne Université, Université de Paris)

  • Simona Cocco

    (Université PSL, CNRS, Sorbonne Université, Université de Paris)

  • Christine Iacobuzio-Donahue

    (Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center)

  • Benjamin D. Greenbaum

    (Memorial Sloan Kettering Cancer Center
    Weill Cornell Medical College)

  • Vinod P. Balachandran

    (Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center)

Abstract

Cancer immunoediting1 is a hallmark of cancer2 that predicts that lymphocytes kill more immunogenic cancer cells to cause less immunogenic clones to dominate a population. Although proven in mice1,3, whether immunoediting occurs naturally in human cancers remains unclear. Here, to address this, we investigate how 70 human pancreatic cancers evolved over 10 years. We find that, despite having more time to accumulate mutations, rare long-term survivors of pancreatic cancer who have stronger T cell activity in primary tumours develop genetically less heterogeneous recurrent tumours with fewer immunogenic mutations (neoantigens). To quantify whether immunoediting underlies these observations, we infer that a neoantigen is immunogenic (high-quality) by two features—‘non-selfness’ based on neoantigen similarity to known antigens4,5, and ‘selfness’ based on the antigenic distance required for a neoantigen to differentially bind to the MHC or activate a T cell compared with its wild-type peptide. Using these features, we estimate cancer clone fitness as the aggregate cost of T cells recognizing high-quality neoantigens offset by gains from oncogenic mutations. With this model, we predict the clonal evolution of tumours to reveal that long-term survivors of pancreatic cancer develop recurrent tumours with fewer high-quality neoantigens. Thus, we submit evidence that that the human immune system naturally edits neoantigens. Furthermore, we present a model to predict how immune pressure induces cancer cell populations to evolve over time. More broadly, our results argue that the immune system fundamentally surveils host genetic changes to suppress cancer.

Suggested Citation

  • Marta Łuksza & Zachary M. Sethna & Luis A. Rojas & Jayon Lihm & Barbara Bravi & Yuval Elhanati & Kevin Soares & Masataka Amisaki & Anton Dobrin & David Hoyos & Pablo Guasp & Abderezak Zebboudj & Rebec, 2022. "Neoantigen quality predicts immunoediting in survivors of pancreatic cancer," Nature, Nature, vol. 606(7913), pages 389-395, June.
  • Handle: RePEc:nat:nature:v:606:y:2022:i:7913:d:10.1038_s41586-022-04735-9
    DOI: 10.1038/s41586-022-04735-9
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41586-022-04735-9
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.

    File URL: https://libkey.io/10.1038/s41586-022-04735-9?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Juan Shen & Xiao Tu & Yuanyuan Li, 2023. "Mathematical Modeling Reveals Mechanisms of Cancer-Immune Interactions Underlying Hepatocellular Carcinoma Development," Mathematics, MDPI, vol. 11(20), pages 1-30, October.
    2. Jiefei Han & Yiting Dong & Xiuli Zhu & Alexandre Reuben & Jianjun Zhang & Jiachen Xu & Hua Bai & Jianchun Duan & Rui Wan & Jie Zhao & Jing Bai & Xuefeng Xia & Xin Yi & Chao Cheng & Jie Wang & Zhijie W, 2024. "Assessment of human leukocyte antigen-based neoantigen presentation to determine pan-cancer response to immunotherapy," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    3. Haodong Xu & Ruifeng Hu & Xianjun Dong & Lan Kuang & Wenchao Zhang & Chao Tu & Zhihong Li & Zhongming Zhao, 2024. "ImmuneApp for HLA-I epitope prediction and immunopeptidome analysis," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:606:y:2022:i:7913:d:10.1038_s41586-022-04735-9. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.