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Distinct molecular and immune hallmarks of inflammatory arthritis induced by immune checkpoint inhibitors for cancer therapy

Author

Listed:
  • Sang T. Kim

    (The University of Texas MD Anderson Cancer Center)

  • Yanshuo Chu

    (The University of Texas MD Anderson Cancer Center)

  • Mercy Misoi

    (Baylor College of Medicine)

  • Maria E. Suarez-Almazor

    (The University of Texas MD Anderson Cancer Center)

  • Jean H. Tayar

    (The University of Texas MD Anderson Cancer Center)

  • Huifang Lu

    (The University of Texas MD Anderson Cancer Center)

  • Maryam Buni

    (The University of Texas MD Anderson Cancer Center)

  • Jordan Kramer

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

  • Emma Rodriguez

    (The University of Texas MD Anderson Cancer Center)

  • Zulekha Hussain

    (The University of Texas MD Anderson Cancer Center)

  • Sattva S. Neelapu

    (The University of Texas MD Anderson Cancer Center)

  • Jennifer Wang

    (The University of Texas MD Anderson Cancer Center)

  • Amishi Y. Shah

    (The University of Texas MD Anderson Cancer Center)

  • Nizar M. Tannir

    (The University of Texas MD Anderson Cancer Center)

  • Matthew T. Campbell

    (The University of Texas MD Anderson Cancer Center)

  • Don L. Gibbons

    (The University of Texas MD Anderson Cancer Center)

  • Tina Cascone

    (The University of Texas MD Anderson Cancer Center)

  • Charles Lu

    (The University of Texas MD Anderson Cancer Center)

  • George R. Blumenschein

    (The University of Texas MD Anderson Cancer Center)

  • Mehmet Altan

    (The University of Texas MD Anderson Cancer Center)

  • Bora Lim

    (The University of Texas MD Anderson Cancer Center)

  • Vincente Valero

    (The University of Texas MD Anderson Cancer Center)

  • Monica E. Loghin

    (The University of Texas MD Anderson Cancer Center)

  • Janet Tu

    (The University of Texas MD Anderson Cancer Center)

  • Shannon N. Westin

    (The University of Texas MD Anderson Cancer Center)

  • Aung Naing

    (The University of Texas MD Anderson Cancer Center)

  • Guillermo Garcia-Manero

    (The University of Texas MD Anderson Cancer Center)

  • Noha Abdel-Wahab

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

  • Hussein A. Tawbi

    (The University of Texas MD Anderson Cancer Center)

  • Patrick Hwu

    (The University of Texas MD Anderson Cancer Center
    H. Lee Moffitt Cancer Center and Research Institute)

  • Isabella C. Glitza Oliva

    (The University of Texas MD Anderson Cancer Center)

  • Michael A. Davies

    (The University of Texas MD Anderson Cancer Center)

  • Sapna P. Patel

    (The University of Texas MD Anderson Cancer Center)

  • Jun Zou

    (The University of Texas MD Anderson Cancer Center)

  • Andrew Futreal

    (The University of Texas MD Anderson Cancer Center)

  • Adi Diab

    (The University of Texas MD Anderson Cancer Center)

  • Linghua Wang

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences (GSBS))

  • Roza Nurieva

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences (GSBS))

Abstract

Immune checkpoint inhibitors are associated with immune-related adverse events (irAEs), including arthritis (arthritis-irAE). Management of arthritis-irAE is challenging because immunomodulatory therapy for arthritis should not impede antitumor immunity. Understanding of the mechanisms of arthritis-irAE is critical to overcome this challenge, but the pathophysiology remains unknown. Here, we comprehensively analyze peripheral blood and/or synovial fluid samples from 20 patients with arthritis-irAE, and unmask a prominent Th1-CD8+ T cell axis in both blood and inflamed joints. CX3CR1hi CD8+ T cells in blood and CXCR3hi CD8+ T cells in synovial fluid, the most clonally expanded T cells, significantly share TCR repertoires. The migration of blood CX3CR1hi CD8+ T cells into joints is possibly mediated by CXCL9/10/11/16 expressed by myeloid cells. Furthermore, arthritis after combined CTLA-4 and PD-1 inhibitor therapy preferentially has enhanced Th17 and transient Th1/Th17 cell signatures. Our data provide insights into the mechanisms, predictive biomarkers, and therapeutic targets for arthritis-irAE.

Suggested Citation

  • Sang T. Kim & Yanshuo Chu & Mercy Misoi & Maria E. Suarez-Almazor & Jean H. Tayar & Huifang Lu & Maryam Buni & Jordan Kramer & Emma Rodriguez & Zulekha Hussain & Sattva S. Neelapu & Jennifer Wang & Am, 2022. "Distinct molecular and immune hallmarks of inflammatory arthritis induced by immune checkpoint inhibitors for cancer therapy," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29539-3
    DOI: 10.1038/s41467-022-29539-3
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    References listed on IDEAS

    as
    1. Thomas Gebhardt & Paul G. Whitney & Ali Zaid & Laura K. Mackay & Andrew G. Brooks & William R. Heath & Francis R. Carbone & Scott N. Mueller, 2011. "Different patterns of peripheral migration by memory CD4+ and CD8+ T cells," Nature, Nature, vol. 477(7363), pages 216-219, September.
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