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

Garrett S. Dunlap, Daniel DiToro, Joel Henderson, Sujal I. Shah, Mike Manos, Mariano Severgnini, Astrid Weins, Indira Guleria, Patrick A. Ott, Naoka Murakami () and Deepak A. Rao ()
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Garrett S. Dunlap: Brigham and Women’s Hospital
Daniel DiToro: Harvard Medical School
Joel Henderson: Boston Medical Center and Boston University
Sujal I. Shah: Harvard Medical School
Mike Manos: Dana-Farber Cancer Institute
Mariano Severgnini: Dana-Farber Cancer Institute
Astrid Weins: Harvard Medical School
Indira Guleria: Harvard Medical School
Patrick A. Ott: Harvard Medical School
Naoka Murakami: Harvard Medical School
Deepak A. Rao: Brigham and Women’s Hospital

Nature Communications, 2023, vol. 14, issue 1, 1-8

Abstract: 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.

Date: 2023
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37230-4

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DOI: 10.1038/s41467-023-37230-4

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