Impact of high-dose chemotherapy on antigen-specific T cell immunity in breast cancer patients. Application of new flow cytometric method.

Abstract:

:The present study analyses the influence of high-dose chemotherapy (HD) and autologous stem cell transplantation on natural and vaccine-induced specific immunity in breast cancer patients. Peripheral blood was collected from five breast cancer patients at serial time points in connection with treatment and in a follow-up period of 1 year. The frequencies of CD8+ and CD4+ T cells responsive to cytomegalovirus (CMV), varicella zoster virus (VZV), and tetanus in antigen-activated whole blood were determined by flow cytometric analysis of CD69, TNF alpha, IFN gamma and IL-4 expression. Mononuclear cells were labelled with PKH26 dye and the CMV, VZV, and tetanus toxoid-specific proliferation of T cell subpopulations was analysed by flow cytometry. In none of the patients did the treatment result in loss of overall T cell reactivity for any of the antigens. Prior to chemotherapy 5/5 patients possessed TNF alpha expressing T cells specific for CMV, 4/5 for VZV, and 3/5 for tetanus. One year after stem cell transplantation all patients possessed TNF alpha expressing T cells specific for CMV, VZV and tetanus. The highest percentages of cytokine-responding T cells were seen after stimulation with CMV antigen. In general, the lowest reactivity (close to zero) was measured in G-CSF-mobilised blood at the time of leukapheresis. In spite of a continuously reduced CD4 to CD8 ratio after transplantation, recovery of CD4+ T cells usually occurred prior to CD8+ recovery and often to a higher level. The study demonstrates that natural as well as vaccine-induced specific immunity established prior to HD can be regained after stem cell transplantation. These data indicate that introduction of a preventive cancer vaccination in combination with intensive chemotherapy may be a realistic treatment option.

journal_name

Bone Marrow Transplant

authors

Svane IM,Nikolajsen K,Hansen SW,Kamby C,Nielsen DL,Johnsen HE

doi

10.1038/sj.bmt.1703521

subject

Has Abstract

pub_date

2002-04-01 00:00:00

pages

659-66

issue

8

eissn

0268-3369

issn

1476-5365

journal_volume

29

pub_type

杂志文章
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    doi:

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    doi:10.1038/sj.bmt.1704105

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    doi:

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    pub_type: 杂志文章

    doi:10.1038/sj.bmt.1703885

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  • Clinically applicable bulk isolation of blood CD34+ cells for autografting in children.

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    pub_type: 临床试验,杂志文章

    doi:10.1038/sj.bmt.1701479

    authors: Kawano Y,Takaue Y,Law P,Watanabe T,Abe T,Okamoto Y,Makimoto A,Sato J,Nakagawa R,Kajiume T,Hirao A,Watanabe A,Kuroda Y

    更新日期:1998-11-01 00:00:00