Cyclophosphamide enhances immunity by modulating the balance of dendritic cell subsets in lymphoid organs

Takeshi Nakahara, Hiroshi Uchi, Alexander M. Lesokhin, Francesca Avogadri, Gabrielle A. Rizzuto, Daniel Hirschhorn-Cymerman, Katherine S. Panageas, Taha Merghoub, Jedd D. Wolchok, Alan N. Houghton

Research output: Contribution to journalArticle

75 Citations (Scopus)

Abstract

Cyclophosphamide (CTX), a commonly used chemotherapeutic agent can enhance immune responses. The ability of CTX to promote the proliferation of effector T cells and abrogate the function of regulatory T cells (Tregs) has been described. In this study, we examined the effects of CTX treatment on dendritic cell (DC) subsets and the subsequent outcome on the effector and suppressive arms of adaptive immunity. In secondary lymphoid tissues, tissue-derived migratory DCs (migratory DCs), lymphoid tissue-resident DCs (resident DCs), and plasmacytoid DCs (pDCs) are well described. CTX has profound and selective cytotoxic effects on CD8+ resident DCs, but not skin-derived migratory DCs or pDCs in lymph nodes (LNs) and spleen, causing an imbalance among these DC subsets. CTX treatment increases the potency of DCs in antigen presentation and cytokine secretion, and partially inhibits the suppressor activity of Tregs. Adoptive transfer of CD8+ DCs can reconstitute this population in regional draining LNs and abrogate the immune-enhancing effects of CTX in vivo. These findings demonstrate that CTX may improve immune responses by preferentially depleting CD8+ lymphoid-resident DCs, which leads to diminished Treg suppression and enhanced effector T-cell function in vivo.

Original languageEnglish
Pages (from-to)4384-4392
Number of pages9
JournalBlood
Volume115
Issue number22
DOIs
Publication statusPublished - Jun 3 2010

Fingerprint

T-cells
Lymphoid Tissue
Cyclophosphamide
Dendritic Cells
Immunity
Lymph Nodes
Tissue
T-Lymphocytes
Adoptive Transfer
Antigen Presentation
Adaptive Immunity
Regulatory T-Lymphocytes
Spleen
Cytokines
Skin
Therapeutics
Population
Antigens

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Nakahara, T., Uchi, H., Lesokhin, A. M., Avogadri, F., Rizzuto, G. A., Hirschhorn-Cymerman, D., ... Houghton, A. N. (2010). Cyclophosphamide enhances immunity by modulating the balance of dendritic cell subsets in lymphoid organs. Blood, 115(22), 4384-4392. https://doi.org/10.1182/blood-2009-11-251231

Cyclophosphamide enhances immunity by modulating the balance of dendritic cell subsets in lymphoid organs. / Nakahara, Takeshi; Uchi, Hiroshi; Lesokhin, Alexander M.; Avogadri, Francesca; Rizzuto, Gabrielle A.; Hirschhorn-Cymerman, Daniel; Panageas, Katherine S.; Merghoub, Taha; Wolchok, Jedd D.; Houghton, Alan N.

In: Blood, Vol. 115, No. 22, 03.06.2010, p. 4384-4392.

Research output: Contribution to journalArticle

Nakahara, T, Uchi, H, Lesokhin, AM, Avogadri, F, Rizzuto, GA, Hirschhorn-Cymerman, D, Panageas, KS, Merghoub, T, Wolchok, JD & Houghton, AN 2010, 'Cyclophosphamide enhances immunity by modulating the balance of dendritic cell subsets in lymphoid organs', Blood, vol. 115, no. 22, pp. 4384-4392. https://doi.org/10.1182/blood-2009-11-251231
Nakahara T, Uchi H, Lesokhin AM, Avogadri F, Rizzuto GA, Hirschhorn-Cymerman D et al. Cyclophosphamide enhances immunity by modulating the balance of dendritic cell subsets in lymphoid organs. Blood. 2010 Jun 3;115(22):4384-4392. https://doi.org/10.1182/blood-2009-11-251231
Nakahara, Takeshi ; Uchi, Hiroshi ; Lesokhin, Alexander M. ; Avogadri, Francesca ; Rizzuto, Gabrielle A. ; Hirschhorn-Cymerman, Daniel ; Panageas, Katherine S. ; Merghoub, Taha ; Wolchok, Jedd D. ; Houghton, Alan N. / Cyclophosphamide enhances immunity by modulating the balance of dendritic cell subsets in lymphoid organs. In: Blood. 2010 ; Vol. 115, No. 22. pp. 4384-4392.
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