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

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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.

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Dunlap, G. S., DiToro, D., Henderson, J., Shah, S. I., Manos, M., Severgnini, M., … Rao, D. A. (2023). Clonal dynamics of alloreactive T cells in kidney allograft rejection after anti-PD-1 therapy. Nature Communications, 14(1). https://doi.org/10.1038/s41467-023-37230-4

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