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Clonal dynamics of alloreactive T cells in kidney allograft rejection after anti-PD-1 therapy

Author

Listed:
  • Garrett S. Dunlap

    (Brigham and Women’s Hospital
    Harvard Medical School)

  • Daniel DiToro

    (Harvard Medical School
    Brigham and Women’s Hospital)

  • Joel Henderson

    (Boston Medical Center and Boston University)

  • Sujal I. Shah

    (Harvard Medical School
    Brigham and Women’s Hospital)

  • Mike Manos

    (Dana-Farber Cancer Institute)

  • Mariano Severgnini

    (Dana-Farber Cancer Institute)

  • Astrid Weins

    (Harvard Medical School
    Brigham and Women’s Hospital)

  • Indira Guleria

    (Harvard Medical School
    Brigham and Women’s Hospital)

  • Patrick A. Ott

    (Harvard Medical School
    Dana-Farber Cancer Institute
    Dana-Farber Cancer Institute
    Broad Institute of MIT and Harvard)

  • Naoka Murakami

    (Harvard Medical School
    Brigham and Women’s Hospital)

  • Deepak A. Rao

    (Brigham and Women’s Hospital
    Harvard Medical School)

Abstract

Kidney transplant recipients are at particular risk for developing tumors, many of which are now routinely treated with immune checkpoint inhibitors (ICIs); however, ICI therapy can precipitate transplant rejection. Here, we use TCR sequencing to identify and track alloreactive T cells in a patient with melanoma who experienced kidney transplant rejection following PD-1 inhibition. The treatment was associated with a sharp increase in circulating alloreactive CD8+ T cell clones, which display a unique transcriptomic signature and were also detected in the rejected kidney but not at tumor sites. Longitudinal and cross-tissue TCR analyses indicate unintended expansion of alloreactive CD8+ T cells induced by ICI therapy for cancer, coinciding with ICI-associated organ rejection.

Suggested Citation

  • Garrett S. Dunlap & Daniel DiToro & Joel Henderson & Sujal I. Shah & Mike Manos & Mariano Severgnini & Astrid Weins & Indira Guleria & Patrick A. Ott & Naoka Murakami & Deepak A. Rao, 2023. "Clonal dynamics of alloreactive T cells in kidney allograft rejection after anti-PD-1 therapy," Nature Communications, Nature, vol. 14(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37230-4
    DOI: 10.1038/s41467-023-37230-4
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