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

Jae Yeo Park, Min Ja Jang, Yoon Hee Chung, Kyung Yong Kim, Sung Su Kim, Won Bok Lee, Seungkwon You, Youn Seok Choi, Dae Young Hur, Daejin Kim

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)


Chemotherapy agents have adverse immunotherapeutic effects secondary to inhibition of hematopoietic stem cell proliferation, particularly in committed lymphoblast. Certain anti-cancer drugs have immuno-modulatory 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-stimulation. 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-CD3ε + 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.

Original languageEnglish
Pages (from-to)1530-1539
Number of pages10
JournalInternational Immunopharmacology
Issue number13-14
Publication statusPublished - 2009 Dec


  • 4-1BB
  • CD4
  • CD40 ligand
  • Doxorubicin

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology


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