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Doxorubicin enhances CD4(+) T-cell immune responses by inducing expression of CD40 ligand and 4-1BB

Authors
Park, Jae YeoJang, Min JaChung, Yoon HeeKim, Kyung YongKim, Sung SuLee, Won BokYou, SeungkwonChoi, Youn SeokHur, Dae YoungKim, Daejin
Issue Date
Dec-2009
Publisher
ELSEVIER SCIENCE BV
Keywords
Doxorubicin; CD4; CD40 ligand; 4-1BB
Citation
INTERNATIONAL IMMUNOPHARMACOLOGY, v.9, no.13-14, pp.1530 - 1539
Indexed
SCIE
SCOPUS
Journal Title
INTERNATIONAL IMMUNOPHARMACOLOGY
Volume
9
Number
13-14
Start Page
1530
End Page
1539
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/118801
DOI
10.1016/j.intimp.2009.09.008
ISSN
1567-5769
Abstract
Chemotherapy agents have adverse immunotherapeutic effects secondary to inhibition of hematopoietic stem cell proliferation, particularly in committed lymphoblast. Certain anti-cancer drugs have immunomodulatory properties, although mechanisms are still not fully understood. In the current study, we explored the effects of doxorubicin on peripheral blood CD4(+) and CD8(+) T-cell responses pre- and post-siimulation. Doxorubicin treatment alone had no effects on peripheral blood T lymphocytes and regulatory T-cells in vivo and in vitro. However, CD4(+) T-cells were resistant to doxorubicin and demonstrated more robust proliferation than CD8(+) T-cells after doxorubicin pre-treatment. CD40 ligand and 4-1BB expression on the surface of CD4(+) T-cells were increased after TCR-ligation activation; however, expression on CD8(+) T-cells was not increased. Dendritic cells cultured in the presence of activated CD4(+) T-cells pre-treated with doxorubicin had greater survival rates than those cultured with activated CD8(+) T-cells. Doxorubicin pre-treatment followed by anti-CD3 epsilon + anti-4-1BB activation led to proliferation of CD4(+) T-cells and no proliferative effects on CD8(+) T-cells. Our results collectively suggest that doxorubicin pre-treatment in cancer patients may be a more effective way to enhance anti-cancer immune responses by increased antigen-specific CD4(+) Th1 immune responses. (C) 2009 Elsevier B.V. All rights reserved.
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