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Depletion of CD25? T cells from hematopoietic stem cell grafts increases posttransplantation vaccine-induced immunity to neuroblastoma.

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.

SUBMITTER: Jing W

PROVIDER: S-EPMC3128485 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

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Depletion of CD25⁺ T cells from hematopoietic stem cell grafts increases posttransplantation vaccine-induced immunity to neuroblastoma.

Jing Weiqing W Yan Xiaocai X Hallett William H D WH Gershan Jill A JA Johnson Bryon D BD

Blood 20110426 25

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 a ...[more]

PMID: 21521781

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Project description:Hematopoietic stem-cell transplantation (HSCT) is a potentially lifesaving therapy for several blood cancers and other diseases. For patients without a suitable related HLA-matched donor, unrelated-donor registries of adult volunteers and banked umbilical cord-blood units, such as the Be the Match Registry operated by the National Marrow Donor Program (NMDP), provide potential sources of donors. Our goal in the present study was to measure the likelihood of finding a suitable donor in the U.S. registry.Using human HLA data from the NMDP donor and cord-blood-unit registry, we built population-based genetic models for 21 U.S. racial and ethnic groups to predict the likelihood of identifying a suitable donor (either an adult donor or a cord-blood unit) for patients in each group. The models incorporated the degree of HLA matching, adult-donor availability (i.e., ability to donate), and cord-blood-unit cell dose.Our models indicated that most candidates for HSCT will have a suitable (HLA-matched or minimally mismatched) adult donor. However, many patients will not have an optimal adult donor--that is, a donor who is matched at high resolution at HLA-A, HLA-B, HLA-C, and HLA-DRB1. The likelihood of finding an optimal donor varies among racial and ethnic groups, with the highest probability among whites of European descent, at 75%, and the lowest probability among blacks of South or Central American descent, at 16%. Likelihoods for other groups are intermediate. Few patients will have an optimal cord-blood unit--that is, one matched at the antigen level at HLA-A and HLA-B and matched at high resolution at HLA-DRB1. However, cord-blood units mismatched at one or two HLA loci are available for almost all patients younger than 20 years of age and for more than 80% of patients 20 years of age or older, regardless of racial and ethnic background.Most patients likely to benefit from HSCT will have a donor. Public investment in donor recruitment and cord-blood banks has expanded access to HSCT. (Funded by the Office of Naval Research, Department of the Navy, and the Health Resources and Services Administration, Department of Health and Human Services.).

Dataset Information

Depletion of CD25? T cells from hematopoietic stem cell grafts increases posttransplantation vaccine-induced immunity to neuroblastoma.

Publications

Depletion of CD25⁺ T cells from hematopoietic stem cell grafts increases posttransplantation vaccine-induced immunity to neuroblastoma.

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