Research ArticleCancer Immunology

CD4+CD25+ Regulatory T Cell Depletion Improves the Graft-Versus-Tumor Effect of Donor Lymphocytes After Allogeneic Hematopoietic Stem Cell Transplantation

Science Translational Medicine  21 Jul 2010:
Vol. 2, Issue 41, pp. 41ra52
DOI: 10.1126/scitranslmed.3001302

You are currently viewing the abstract.

View Full Text
As a service to the community, AAAS/Science has made this article free with registration.

Abstract

Donor T cells play a pivotal role in the graft-versus-tumor effect after allogeneic hematopoietic stem cell transplantation. Regulatory T cells (Tregs) may reduce alloreactivity, the major component of the graft-versus-tumor effect. In the setting of donor lymphocyte infusion after hematopoietic stem cell transplantation, we postulated that Treg depletion could improve alloreactivity and likewise the graft-versus-tumor effect of donor T cells. The safety and efficacy of Treg-depleted donor lymphocyte infusion was studied in 17 adult patients with malignancy relapse after hematopoietic stem cell transplantation. All but one had previously failed to respond to at least one standard donor lymphocyte infusion, and none had experienced graft-versus-host disease. Two of the 17 patients developed graft-versus-host disease after their first Treg-depleted donor lymphocyte infusion and experienced a long-term remission of their malignancy. Four of the 15 patients who did not respond after a first Treg-depleted donor lymphocyte infusion received a second Treg-depleted donor lymphocyte infusion combined with lymphodepleting chemotherapy aimed to also eliminate recipient Tregs. All four developed acute-like graft-versus-host disease that was associated with a partial or complete and durable remission. In the whole cohort, graft-versus-host disease induction through Treg depletion was associated with improved survival. These results suggest that Treg-depleted donor lymphocyte infusion is a safe, feasible approach that induces graft-versus-host or graft-versus-tumor effects in alloreactivity-resistant patients. In patients not responding to this approach, the combination of chemotherapy-induced lymphodepletion of the recipient synergizes with the effect of Treg-depleted donor lymphocyte infusion. These findings offer a rational therapeutic approach for cancer cellular immunotherapy.

Footnotes

  • These authors contributed equally to this work.

  • These authors contributed equally to this work.

  • Citation: S. Maury, F. M. Lemoine, Y. Hicheri, M. Rosenzwajg, C. Badoual, M. Cheraï, J.-L. Beaumont, N. Azar, N. Dhedin, A. Sirvent, A. Buzyn, M.-T. Rubio, S. Vigouroux, O. Montagne, D. Bories, F. Roudot- Thoraval, J.-P. Vernant, C. Cordonnier, D. Klatzmann, J. L. Cohen, CD4+CD25+ regulatory T cell depletion improves the graft-versus-tumor effect of donor lymphocytes after allogeneic hematopoietic stem cell transplantation.Sci. Transl. Med. 2, 41ra52 (2010).

View Full Text