Clonal dynamics of alloreactive T cells in kidney allograft rejection after anti-PD-1 therapy [MLR single-cell]

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. We utilized TCR sequencing to identify and track alloreactive T cells in a patient with melanoma who experienced kidney transplant rejection following ICI therapy. ICI therapy was associated with a sharp increase in circulating alloreactive CD8+ T cell clones, many of which were also detected in the rejected kidney but not at tumor sites. Longitudinal and cross-tissue TCR analyses revealed unintended expansion of alloreactive CD8+ T cells induced by ICI therapy for cancer, coinciding with ICI-associated organ rejection. A mixed-lymphocyte reaction (MLR) was performed using donor splenocytes and recipient (post-pembro) PBMCs to identify alloreactive T cells, and paired single-cell RNA and TCR sequencing was used to link proliferative and transcriptomic states with TCR clone. *** Submitter declares that the human samples require control for access and will be uploaded to dbGaP. ***