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Evolution and modulation of antigen-specific T cell responses in melanoma patients

Author

Listed:
  • Jani Huuhtanen

    (University of Helsinki
    Helsinki University Hospital Comprehensive Cancer Center
    iCAN Digital Precision Cancer Medicine Flagship
    Aalto University)

  • Liang Chen

    (Stanford University
    Stanford University School of Medicine)

  • Emmi Jokinen

    (Aalto University)

  • Henna Kasanen

    (University of Helsinki
    Helsinki University Hospital Comprehensive Cancer Center
    iCAN Digital Precision Cancer Medicine Flagship)

  • Tapio Lönnberg

    (University of Turku and Åbo Akademi University
    University of Turku)

  • Anna Kreutzman

    (University of Helsinki
    Helsinki University Hospital Comprehensive Cancer Center
    iCAN Digital Precision Cancer Medicine Flagship)

  • Katriina Peltola

    (iCAN Digital Precision Cancer Medicine Flagship
    Helsinki University Hospital Comprehensive Cancer Center)

  • Micaela Hernberg

    (Helsinki University Hospital Comprehensive Cancer Center)

  • Chunlin Wang

    (Stanford University
    Stanford University School of Medicine)

  • Cassian Yee

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Harri Lähdesmäki

    (Aalto University)

  • Mark M. Davis

    (Stanford University
    Stanford University School of Medicine
    Stanford University School of Medicine)

  • Satu Mustjoki

    (University of Helsinki
    Helsinki University Hospital Comprehensive Cancer Center
    iCAN Digital Precision Cancer Medicine Flagship
    University of Helsinki)

Abstract

Analyzing antigen-specific T cell responses at scale has been challenging. Here, we analyze three types of T cell receptor (TCR) repertoire data (antigen-specific TCRs, TCR-repertoire, and single-cell RNA + TCRαβ-sequencing data) from 515 patients with primary or metastatic melanoma and compare it to 783 healthy controls. Although melanoma-associated antigen (MAA) -specific TCRs are restricted to individuals, they share sequence similarities that allow us to build classifiers for predicting anti-MAA T cells. The frequency of anti-MAA T cells distinguishes melanoma patients from healthy and predicts metastatic recurrence from primary melanoma. Anti-MAA T cells have stem-like properties and frequent interactions with regulatory T cells and tumor cells via Galectin9-TIM3 and PVR-TIGIT -axes, respectively. In the responding patients, the number of expanded anti-MAA clones are higher after the anti-PD1(+anti-CTLA4) therapy and the exhaustion phenotype is rescued. Our systems immunology approach paves the way for understanding antigen-specific responses in human disorders.

Suggested Citation

  • Jani Huuhtanen & Liang Chen & Emmi Jokinen & Henna Kasanen & Tapio Lönnberg & Anna Kreutzman & Katriina Peltola & Micaela Hernberg & Chunlin Wang & Cassian Yee & Harri Lähdesmäki & Mark M. Davis & Sat, 2022. "Evolution and modulation of antigen-specific T cell responses in melanoma patients," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33720-z
    DOI: 10.1038/s41467-022-33720-z
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    1. Paul C. Tumeh & Christina L. Harview & Jennifer H. Yearley & I. Peter Shintaku & Emma J. M. Taylor & Lidia Robert & Bartosz Chmielowski & Marko Spasic & Gina Henry & Voicu Ciobanu & Alisha N. West & M, 2014. "PD-1 blockade induces responses by inhibiting adaptive immune resistance," Nature, Nature, vol. 515(7528), pages 568-571, November.
    2. Florian Rubelt & Christopher R. Bolen & Helen M. McGuire & Jason A. Vander Heiden & Daniel Gadala-Maria & Mikhail Levin & Ghia M. Euskirchen & Murad R. Mamedov & Gary E. Swan & Cornelia L. Dekker & Li, 2016. "Individual heritable differences result in unique cell lymphocyte receptor repertoires of naïve and antigen-experienced cells," Nature Communications, Nature, vol. 7(1), pages 1-12, June.
    3. Yannick Simoni & Etienne Becht & Michael Fehlings & Chiew Yee Loh & Si-Lin Koo & Karen Wei Weng Teng & Joe Poh Sheng Yeong & Rahul Nahar & Tong Zhang & Hassen Kared & Kaibo Duan & Nicholas Ang & Micha, 2018. "Bystander CD8+ T cells are abundant and phenotypically distinct in human tumour infiltrates," Nature, Nature, vol. 557(7706), pages 575-579, May.
    4. Mikhail Shugay & Dmitriy V Bagaev & Maria A Turchaninova & Dmitriy A Bolotin & Olga V Britanova & Ekaterina V Putintseva & Mikhail V Pogorelyy & Vadim I Nazarov & Ivan V Zvyagin & Vitalina I Kirgizova, 2015. "VDJtools: Unifying Post-analysis of T Cell Receptor Repertoires," PLOS Computational Biology, Public Library of Science, vol. 11(11), pages 1-16, November.
    5. Michael A. Durante & Daniel A. Rodriguez & Stefan Kurtenbach & Jeffim N. Kuznetsov & Margaret I. Sanchez & Christina L. Decatur & Helen Snyder & Lynn G. Feun & Alan S. Livingstone & J. William Harbour, 2020. "Single-cell analysis reveals new evolutionary complexity in uveal melanoma," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
    6. Christopher S. Carlson & Ryan O. Emerson & Anna M. Sherwood & Cindy Desmarais & Moon-Wook Chung & Joseph M. Parsons & Michelle S. Steen & Marissa A. LaMadrid-Herrmannsfeldt & David W. Williamson & Rob, 2013. "Using synthetic templates to design an unbiased multiplex PCR assay," Nature Communications, Nature, vol. 4(1), pages 1-9, December.
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