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
04/28/2011Pubmed ID
21521781Pubmed Central ID
PMC3128485DOI
10.1182/blood-2010-12-326108Scopus ID
2-s2.0-79959507720 (requires institutional sign-in at Scopus site) 37 CitationsAbstract
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 BDAuthor
Bryon D. Johnson PhD Adjunct Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCD4-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
