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Stroma-infiltrating T cell spatiotypes define immunotherapy outcomes in adolescent and young adult patients with melanoma

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Listed:
  • Xinyu Bai

    (The University of Sydney
    The University of Sydney
    The University of Sydney)

  • Grace H. Attrill

    (The University of Sydney
    The University of Sydney
    The University of Sydney)

  • Tuba N. Gide

    (The University of Sydney
    The University of Sydney
    The University of Sydney)

  • Peter M. Ferguson

    (The University of Sydney
    The University of Sydney
    Royal Prince Alfred Hospital
    NSW Health Pathology)

  • Kazi J. Nahar

    (The University of Sydney
    The University of Sydney
    The University of Sydney)

  • Ping Shang

    (The University of Sydney
    The University of Sydney
    The University of Sydney)

  • Ismael A. Vergara

    (The University of Sydney
    The University of Sydney
    The University of Sydney)

  • Umaimainthan Palendira

    (The University of Sydney
    The University of Sydney
    The University of Sydney
    The University of Sydney)

  • Ines Pires Silva

    (The University of Sydney
    The University of Sydney
    The University of Sydney
    Westmead and Blacktown Hospitals)

  • Matteo S. Carlino

    (The University of Sydney
    Westmead and Blacktown Hospitals)

  • Alexander M. Menzies

    (The University of Sydney
    The University of Sydney
    Royal North Shore Hospital
    Mater Hospital)

  • Georgina V. Long

    (The University of Sydney
    The University of Sydney
    The University of Sydney
    Royal North Shore Hospital)

  • Richard A. Scolyer

    (The University of Sydney
    The University of Sydney
    The University of Sydney
    Royal Prince Alfred Hospital)

  • James S. Wilmott

    (The University of Sydney
    The University of Sydney
    The University of Sydney)

  • Camelia Quek

    (The University of Sydney
    The University of Sydney
    The University of Sydney)

Abstract

The biological underpinnings of therapeutic resistance to immune checkpoint inhibitors (ICI) in adolescent and young adult (AYA) melanoma patients are incompletely understood. Here, we characterize the immunogenomic profile and spatial architecture of the tumor microenvironment (TME) in AYA (aged ≤ 30 years) and older adult (aged 31–84 years) patients with melanoma, to determine the AYA-specific features associated with ICI treatment outcomes. We identify two ICI-resistant spatiotypes in AYA patients with melanoma showing stroma-infiltrating lymphocytes (SILs) that are distinct from the adult TME. The SILhigh subtype was enriched in regulatory T cells in the peritumoral space and showed upregulated expression of immune checkpoint molecules, while the SILlow subtype showed a lack of immune activation. We establish a young immunosuppressive melanoma score that can predict ICI responsiveness in AYA patients and propose personalized therapeutic strategies for the ICI-resistant subgroups. These findings highlight the distinct immunogenomic profile of AYA patients, and individualized TME features in ICI-resistant AYA melanoma that require patient-specific treatment strategies.

Suggested Citation

  • Xinyu Bai & Grace H. Attrill & Tuba N. Gide & Peter M. Ferguson & Kazi J. Nahar & Ping Shang & Ismael A. Vergara & Umaimainthan Palendira & Ines Pires Silva & Matteo S. Carlino & Alexander M. Menzies , 2024. "Stroma-infiltrating T cell spatiotypes define immunotherapy outcomes in adolescent and young adult patients with melanoma," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47301-9
    DOI: 10.1038/s41467-024-47301-9
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