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Depletion of CD25⁺ T cells from hematopoietic stem cell grafts increases posttransplantation vaccine-induced immunity to neuroblastoma. Blood 2011 Jun 23;117(25):6952-62

Date

04/28/2011

Pubmed ID

21521781

Pubmed Central ID

PMC3128485

DOI

10.1182/blood-2010-12-326108

Scopus ID

2-s2.0-79959507720   30 Citations

Abstract

A multifaceted immunotherapeutic strategy that includes hematopoietic stem cell (HSC) transplantation, T-cell adoptive transfer, and tumor vaccination can effectively eliminate established neuroblastoma tumors in mice. In vivo depletion of CD4⁺ T cells in HSC transplantation recipients results in increased antitumor immunity when adoptively transferred T cells are presensitized, but development of T-cell memory is severely compromised. Because increased percentages of regulatory T (Treg) cells are seen in HSC transplantation recipients, here we hypothesized that the inhibitory effect of CD4⁺ T cells is primarily because of the presence of expanded Treg cells. Remarkably, adoptive transfer of presensitized CD25-depleted T cells increased tumor vaccine efficacy. The enhanced antitumor effect achieved by ex vivo depletion of CD25⁺ Treg cells was similar to that achieved by in vivo depletion of all CD4⁺ T cells. Depletion of CD25⁺ Treg cells resulted in elevated frequencies of tumor-reactive CD8 and CD4⁺ T cells and increased CD8-to-Treg cell ratios inside tumor masses. All mice given presensitized CD25-depleted T cells survived a tumor rechallenge, indicating the development of long-term CD8⁺ T-cell memory to tumor antigens. These observations should aid in the future design of immunotherapeutic approaches that promote the generation of both acute and long-term antitumor immunity.

Author List

Jing W, Yan X, Hallett WH, Gershan JA, Johnson BD

Author

Bryon D. Johnson PhD Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Cancer Vaccines
Hematopoietic Stem Cell Transplantation
Hepatocyte Nuclear Factor 3-gamma
Immunotherapy, Adoptive
Interleukin-2 Receptor alpha Subunit
Mice
Neuroblastoma
T-Lymphocytes
T-Lymphocytes, Regulatory
jenkins-FCD Prod-403 0f9a74600e4e79798f8fa6f545ea115f3dd948b2