title: 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.
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 FoxP3CD25, FoxP3CD127, or CD4CD127 Treg cells (P=0.04). The CD4CD127 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 CD4CD127 phenotype of Treg could be particularly relevant to manipulate this cell-population, to increase the antitumoral response in strategies of allogeneic or autologous immunotherapy.
authors.affiliation: AP-HP, Groupe Henri-Mondor Albert-Chenevier, Service d'Hématologie Clinique, Universite Paris 12, Paris, France.
authors.forename: Yosr
authors.initials: Y
authors.lastname: Hicheri
authors.forename: Abdelghani
authors.initials: A
authors.lastname: Bouchekioua
authors.forename: Yamina
authors.initials: Y
authors.lastname: Hamel
authors.forename: Adeline
authors.initials: A
authors.lastname: Henry
authors.forename: Hélène
authors.initials: H
authors.lastname: Rouard
authors.forename: Cécile
authors.initials: C
authors.lastname: Pautas
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Beaumont
authors.forename: Mathieu
authors.initials: M
authors.lastname: Kuentz
authors.forename: Catherine
authors.initials: C
authors.lastname: Cordonnier
authors.forename: José L
authors.initials: JL
authors.lastname: Cohen
authors.forename: Sébastien
authors.initials: S
authors.lastname: Maury
mesh_terms: D000328:Adult; D000368:Aged; D015704:CD4 Antigens; D003602:Cytotoxicity, Immunologic; D005260:Female; D005500:Follow-Up Studies; D051858:Forkhead Transcription Factors; D006086:Graft vs Host Disease / Q000276:immunology; D020350:Graft vs Tumor Effect / Q000276:immunology*; D006801:Humans; D016219:Immunotherapy, Adoptive; D053699:Interleukin-7 Receptor alpha Subunit / Q000235:genetics / Q000378:metabolism; D007951:Leukemia, Myeloid / Q000473:pathology* / Q000628:therapy; D017710:Lymphocyte Transfusion; D008297:Male; D008875:Middle Aged; D033581:Stem Cell Transplantation; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*
chemical_list: D015704:CD4 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053699:Interleukin-7 Receptor alpha Subunit