Work

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

Year: 2023

Type: article

Study design: Case Report

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.

Source: Nature Communications

DOI: 10.1038/s41467-023-37230-4

Authors: 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

Institutions: Brigham and Women's Hospital, Harvard University, Boston University, Boston Medical Center, Dana-Farber Cancer Institute, Broad Institute

Language: English

Topic: Renal Transplantation Outcomes and Treatments

Subfield: Transplantation

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $6,290

Funders: U.S. Department of Health and Human Services, Burroughs Wellcome Fund, American Society of Nephrology, National Institutes of Health, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases

Awards: G1159304973, Protection of kidney from autoimmunity by modulating co-stimlatory signaling, G2477827702, Role of antigen-specific T cells in immunotherapy-associated acute interstitial nephritis and kidney allograft rejection, G4885669581, G4969162889, G5604055329, G5867270196, Molecular control of CD4 T cell ability to help B cells, Dissecting neoepitope-specific clonal T cell populations in advanced melanoma patients vaccinated with personal neoantigen peptides partnered with local and systemic immune checkpoint Inhibition, G9000066119, G9000167209, G9000286667, Joint Biology Consortium Resource-based Center, G998306701

OpenAlex ID: W4328048840

FWCI: 8.165

Cites: 28

Cited by: 32

Related to: 10