Amplification of tumor-specific regulatory T cells following therapeutic cancer vaccines

Gang Zhou, Charles G. Drake, Hyam I. Levitsky

Research output: Contribution to journalArticle

237 Citations (Scopus)

Abstract

The fate of tumor-specific CD4+ T cells is central to the outcome of the host immune response to cancer. We show that tumor antigen recognition by a subset of CD4+ T cells led to their differentiation into cells capable of suppressing naive and Th1 effector cells. Such tumor-induced regulatory T cells (TMTregs) arose both from precommitted "natural" regulatory T cells and CD4+CD25 -GITRlow precursors. Once induced, TMTregs were capable of maintaining suppressor activity long after transfer into antigen-free recipients. Suppression was mediated by GITRhigh cells residing within both CD25+ and CD25- subsets. Vaccination of the tumor-bearing host concomitantly expanded TMTregs and effector cells, but suppression was dominant, blunting the expansion of naive tumor-specific T cells and blocking the execution of effector function in vitro and in vivo. These studies illustrate the possibility that therapeutic vaccination could actually worsen host tolerance to tumor antigens and support treatment paradigms that seek to not only increase the frequency of tumor-specific T cells, but to do so in conjunction with strategies that inactivate or remove regulatory T-cell populations.

Original languageEnglish (US)
Pages (from-to)628-636
Number of pages9
JournalBlood
Volume107
Issue number2
DOIs
StatePublished - Jan 15 2006
Externally publishedYes

Fingerprint

Cancer Vaccines
T-cells
Regulatory T-Lymphocytes
Amplification
Tumors
Neoplasms
Neoplasm Antigens
T-Lymphocytes
Vaccination
Therapeutics
Bearings (structural)
Th1 Cells
T-Lymphocyte Subsets
Cell Differentiation
Antigens
Population

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Amplification of tumor-specific regulatory T cells following therapeutic cancer vaccines. / Zhou, Gang; Drake, Charles G.; Levitsky, Hyam I.

In: Blood, Vol. 107, No. 2, 15.01.2006, p. 628-636.

Research output: Contribution to journalArticle

Zhou, Gang ; Drake, Charles G. ; Levitsky, Hyam I. / Amplification of tumor-specific regulatory T cells following therapeutic cancer vaccines. In: Blood. 2006 ; Vol. 107, No. 2. pp. 628-636.
@article{b5568e216e67463b9d772d6523b3a01a,
title = "Amplification of tumor-specific regulatory T cells following therapeutic cancer vaccines",
abstract = "The fate of tumor-specific CD4+ T cells is central to the outcome of the host immune response to cancer. We show that tumor antigen recognition by a subset of CD4+ T cells led to their differentiation into cells capable of suppressing naive and Th1 effector cells. Such tumor-induced regulatory T cells (TMTregs) arose both from precommitted {"}natural{"} regulatory T cells and CD4+CD25 -GITRlow precursors. Once induced, TMTregs were capable of maintaining suppressor activity long after transfer into antigen-free recipients. Suppression was mediated by GITRhigh cells residing within both CD25+ and CD25- subsets. Vaccination of the tumor-bearing host concomitantly expanded TMTregs and effector cells, but suppression was dominant, blunting the expansion of naive tumor-specific T cells and blocking the execution of effector function in vitro and in vivo. These studies illustrate the possibility that therapeutic vaccination could actually worsen host tolerance to tumor antigens and support treatment paradigms that seek to not only increase the frequency of tumor-specific T cells, but to do so in conjunction with strategies that inactivate or remove regulatory T-cell populations.",
author = "Gang Zhou and Drake, {Charles G.} and Levitsky, {Hyam I.}",
year = "2006",
month = "1",
day = "15",
doi = "10.1182/blood-2005-07-2737",
language = "English (US)",
volume = "107",
pages = "628--636",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "2",

}

TY - JOUR

T1 - Amplification of tumor-specific regulatory T cells following therapeutic cancer vaccines

AU - Zhou, Gang

AU - Drake, Charles G.

AU - Levitsky, Hyam I.

PY - 2006/1/15

Y1 - 2006/1/15

N2 - The fate of tumor-specific CD4+ T cells is central to the outcome of the host immune response to cancer. We show that tumor antigen recognition by a subset of CD4+ T cells led to their differentiation into cells capable of suppressing naive and Th1 effector cells. Such tumor-induced regulatory T cells (TMTregs) arose both from precommitted "natural" regulatory T cells and CD4+CD25 -GITRlow precursors. Once induced, TMTregs were capable of maintaining suppressor activity long after transfer into antigen-free recipients. Suppression was mediated by GITRhigh cells residing within both CD25+ and CD25- subsets. Vaccination of the tumor-bearing host concomitantly expanded TMTregs and effector cells, but suppression was dominant, blunting the expansion of naive tumor-specific T cells and blocking the execution of effector function in vitro and in vivo. These studies illustrate the possibility that therapeutic vaccination could actually worsen host tolerance to tumor antigens and support treatment paradigms that seek to not only increase the frequency of tumor-specific T cells, but to do so in conjunction with strategies that inactivate or remove regulatory T-cell populations.

AB - The fate of tumor-specific CD4+ T cells is central to the outcome of the host immune response to cancer. We show that tumor antigen recognition by a subset of CD4+ T cells led to their differentiation into cells capable of suppressing naive and Th1 effector cells. Such tumor-induced regulatory T cells (TMTregs) arose both from precommitted "natural" regulatory T cells and CD4+CD25 -GITRlow precursors. Once induced, TMTregs were capable of maintaining suppressor activity long after transfer into antigen-free recipients. Suppression was mediated by GITRhigh cells residing within both CD25+ and CD25- subsets. Vaccination of the tumor-bearing host concomitantly expanded TMTregs and effector cells, but suppression was dominant, blunting the expansion of naive tumor-specific T cells and blocking the execution of effector function in vitro and in vivo. These studies illustrate the possibility that therapeutic vaccination could actually worsen host tolerance to tumor antigens and support treatment paradigms that seek to not only increase the frequency of tumor-specific T cells, but to do so in conjunction with strategies that inactivate or remove regulatory T-cell populations.

UR - http://www.scopus.com/inward/record.url?scp=30444443314&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=30444443314&partnerID=8YFLogxK

U2 - 10.1182/blood-2005-07-2737

DO - 10.1182/blood-2005-07-2737

M3 - Article

C2 - 16179369

AN - SCOPUS:30444443314

VL - 107

SP - 628

EP - 636

JO - Blood

JF - Blood

SN - 0006-4971

IS - 2

ER -