Tumor antigen specific iTreg accumulate in the tumor microenvironment and suppress therapeutic vaccination

Taylor H. Schreiber, Dietlinde Wolf, Maria Bodero, Eckhard R. Podack

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Tumor specific antigens (TSA) provide an opportunity to mobilize therapeutic immune responses against cancer. To evade such responses, tumor development in immunocompetent hosts is accompanied by acquisition of both active and passive mechanisms of immune suppression, including recruitment of CD4+FoxP3+ regulatory T cells (Treg). Thymic derived Treg (nTreg) may recognize self-antigens in the tumor microenvironment, while peripherally induced Treg (iTreg) may preferentially recognize the same TSA which provide an opportunity for therapeutic immunity from peripheral T cells. In this study we provide a systematic analysis of nTreg and iTreg accumulation in the tumor microenvironment (TME) at the cellular level. iTreg accumulation to the TME was influenced by the abundance of a known TSA, and in the absence of a known TSA intratumoral Treg displayed a unique TCR repertoire from peripheral Treg. In vivo suppression assays demonstrate that cognate-antigen matched iTreg are more potent suppressors of CD4+ than are polyclonal iTreg or nTreg, but were unable to suppress CD8+ T-cell proliferation. Suppression occurred only locally at the site of immunization, and correlated with decreased expression of CD80 and CD86 on CD11c positive cells. Although established tumors facilitated the induction of TSA -specific iTreg, these iTreg suppressed CD4+ T-cell accumulation only locally to the TME. Tumor mediated suppression of CD8+ T-cell immunity appeared independent of TSA -specific iTreg.

Original languageEnglish (US)
Pages (from-to)642-648
Number of pages7
JournalOncoImmunology
Volume1
Issue number5
DOIs
StatePublished - 2012

Keywords

  • FoxP3
  • iTreg
  • nTreg
  • Regulatory T cell
  • Tumor microenvironment

ASJC Scopus subject areas

  • Immunology and Allergy
  • Oncology
  • Immunology

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