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, Deepak A. Rao
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.