Donor Regulatory T Cells Identified by FoxP3 Expression but Also by the Membranous CD4+CD127low/neg Phenotype Influence Graft-versus-tumor Effect After Donor Lymphocyte Infusion


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Abstract

Regulatory T cells (Treg) play a pivotal role in the control of graft-versus-host disease (GVHD) and might also influence the graft-versus-tumor effect after allogeneic stem cell transplantation. We assessed this role after donor lymphocyte infusions (DLIs) by quantifying Treg in DLI products, using the CD25, Foxp3 but also the recently identified CD127 Treg markers. Compared with others, patients in durable complete remission of their malignancy after DLI had received a lower number of FoxP3+CD25+, FoxP3+CD127low/neg, or CD4+CD127low/neg Treg cells (P=0.04). The CD4+CD127low/neg Treg content of DLI remained significantly correlated with the hematologic response in multivariate analysis (P=0.05). Treg may thus inhibit graft-versus-tumor effect after DLI, a setting where the antitumoral effect observed is only driven by T-cell–mediated cytotoxicity, independently of any other associated treatment. In comparison with the intracytoplasmic Foxp3 marker, the membranous CD4+CD127low/neg phenotype of Treg could be particularly relevant to manipulate this cell-population, to increase the antitumoral response in strategies of allogeneic or autologous immunotherapy.

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