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

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. Immune checkpoint inhibitors (ICI) may have unanticipated side effects in transplant recipients who subsequently develop tumors. Here the authors used single-cell sequencing to identify and characterize allogeneic reactive T cells that developed after an ICI course for melanoma in a transplant recipient.

Automated summary

Kidney transplant recipients are at risk for tumors and are often treated with immune checkpoint inhibitors (ICIs), but this therapy can lead to transplant rejection. In this study, TCR sequencing was used to track and identify alloreactive T cells in a melanoma patient who experienced kidney transplant rejection after PD-1 inhibition. The patient showed an increase in alloreactive CD8(+) T cell clones in the blood, which had a unique transcriptomic signature and were also found in the rejected kidney but not in tumor sites. Longitudinal and cross-tissue TCR analyses revealed unintended expansion of alloreactive CD8(+) T cells induced by ICI therapy, coinciding with organ rejection.