To improve transplantation outcomes, the impact of donor graft T cell subsets on the clinical outcome after HSCT has been studied. Although its efficacy has evolved in the last years, the procedure is still associated with substantial transplant-related morbidity, mainly underlying disease relapse, graft-versus-host disease (GvHD), and infections ( 2). Hematopoietic stem cell transplantation (HSCT) has been used for decades to treat a wide range of hematological malignancies, such as acute myeloid leukemia (AML) ( 1). Our findings show that, despite CMV infection reshaping the TRG repertoire, TRG composition is not associated with aGvHD development, and several public sequences are associated with clinical remission. Our work identified five private overrepresented and one public CDR3 sequence (CATWDGPYYKKLF) associated with CMV infection, in addition to 12 highly frequent public sequences present exclusively in grafts given to nonrelapse patients. Variable-joining gene segment usage was not associated with aGvHD development, but a higher usage of V2-JP1 pairing and lower usage of V4-J2/V5-J2/V8-JP2 were observed in grafts given to nonrelapse patients. Grafts given to nonrelapse patients presented a more public repertoire and increased presence of long sequence clonotypes. This was more prominent in grafts from CMV + donors, which presented a more private repertoire, lower diversity, skewed distribution, and reduced usage of the V9-JP pairing.
In all samples, TRG repertoire showed a reduced diversity and displayed overrepresented clones. The respective acute myeloid leukemia recipients were followed for disease relapse and acute graft-versus-host disease (aGvHD) development post-HSCT. A total of 20 peripheral blood stem cell grafts were analyzed, and donors were classified as CMV +/−. Using a high-throughput sequencing platform, we sought to analyze the TCR γ-chain (TRG) repertoire of γδ T cells within donor stem cell grafts and address its potential impact on clinical response in the corresponding patients. Although the impact of donor graft composition on clinical outcomes after hematopoietic stem cell transplantation (HSCT) has been studied, little is known about the role of intragraft γδ TCR repertoire on clinical outcomes following HSCT.
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