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Dunlap, Garrett S; DiToro, Daniel; Henderson, Joel; Shah, Sujal I; Manos, Mike; Severgnini, Mariano; Weins, Astrid; Guleria, Indira; Ott, Patrick A; Murakami, Naoka; Rao, Deepak A
Nature communications, 03/2023, Volume: 14, Issue: 1Journal Article
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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