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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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