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

Autor: Dunlap GS; Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA., DiToro D; Harvard Medical School, Boston, MA, USA.; Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA., Henderson J; Department of Pathology, Boston Medical Center and Boston University, Boston, MA, USA., Shah SI; Harvard Medical School, Boston, MA, USA.; Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA., Manos M; Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Severgnini M; Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Weins A; Harvard Medical School, Boston, MA, USA.; Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA., Guleria I; Harvard Medical School, Boston, MA, USA.; Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA., Ott PA; Harvard Medical School, Boston, MA, USA.; Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA., Murakami N; Harvard Medical School, Boston, MA, USA. nmurakami1@bwh.harvard.edu.; Division of Renal Medicine, Brigham and Women's Hospital, Boston, MA, USA. nmurakami1@bwh.harvard.edu., Rao DA; Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, Boston, MA, USA. darao@bwh.harvard.edu.; Harvard Medical School, Boston, MA, USA. darao@bwh.harvard.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Mar 21; Vol. 14 (1), pp. 1549. Date of Electronic Publication: 2023 Mar 21.
DOI: 10.1038/s41467-023-37230-4
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
Externí odkaz: