Levels of peripheral CD4 +FoxP3 + regulatory T cells are negatively associated with clinical response to adoptive immunotherapy of human cancer

Xin Yao, Mojgan Ahmadzadeh, Yong Chen Lu, David J. Liewehr, Mark E. Dudley, Fang Liu, David S. Schrump, Seth M. Steinberg, Steven A. Rosenberg, Paul F. Robbins

Research output: Contribution to journalArticle

Abstract

CD4 +FoxP3 + regulatory T cells (Tregs) have been shown to suppress T cell-mediated host immune responses against self- and nonself-antigens; however, the impact of CD4 + Tregs on human antitumor immune responses and their influence on cancer treatment are unknown. In the present study, we explored the factors that influence CD4 + Treg reconstitution in patients receiving adoptive immunotherapy following conditioning regimens designed to enhance T-cell function and evaluated potential associations between CD4 + Treg levels and clinical responses to therapy. The analysis of 4 trials employing nonmyeloablative chemotherapy with or without total body irradiation (TBI) before adoptive T-cell transfer revealed that the percentage and number of reconstituting CD4 +FoxP3 + Tregs observed in the peripheral blood was higher in nonresponders than in responders. The addition of TBI resulted in a further depletion of CD4 + Tregs, and the degree of depletion was dependent on the TBI dose. The number of administered doses of IL-2 was found to be positively associated with peripheral Treg reconstitution. These observations provide strong evidence that endogenous CD4 + Tregs have a negative impact on cancer therapy, and suggest that strategies reducing Treg levels may provide clinical benefit to cancer patients. All 5 clinical trials are registered at www.clinicaltrials.gov as NCT00001832, NCT00096382, NCT00335127, NCT00509496, and NCT00513604.

Original languageEnglish (US)
Pages (from-to)5688-5696
Number of pages9
JournalBlood
Volume119
Issue number24
DOIs
StatePublished - Jun 14 2012

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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