Clinical significance of defective dendritic cell differentiation in cancer

Bond Almand, John R. Resser, Brian Lindman, Sorena Nadaf, Joseph I. Clark, Eugene D Kwon, David P. Carbone, Dmitry I. Gabrilovich

Research output: Contribution to journalArticle

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Abstract

Defective dendritic cell (DC) function has been described previously in cancer patients and tumor-bearing mice. It can be an important factor in the escape of tumors from immune system control. However, the mechanism and clinical significance of this phenomenon remain unclear. Here, 93 patients with breast, head and neck, and lung cancer were investigated. The function of peripheral blood and tumor draining lymph node DCs was equally impaired in cancer patients, consistent with a systemic rather than a local effect of tumor on DCs. The number of DCs was dramatically reduced in the peripheral blood of cancer patients. This decrease was associated with the accumulation of cells lacking markers of mature hematopoietic cells. The presence of these immature cells was closely associated with the stage and duration of the disease. Surgical removal of tumor resulted in partial reversal of the observed effects. The presence of immature cells in the peripheral blood of cancer patients was closely associated with an increased plasma level of vascular endothelial growth factor but not interleukin 6, granulocyte macrophage colony-stimulating factor, macrophage colony-stimulating factor, interleukin 10, or transforming growth factor-β and was decreased in lung cancer patients receiving therapy with antivascular endothelial growth factor antibodies. These data indicate that defective DC function in cancer patients is the result of decreased numbers of competent DCs and the accumulation of immature cells. This effect may have significant clinical implications.

Original languageEnglish (US)
Pages (from-to)1755-1766
Number of pages12
JournalClinical Cancer Research
Volume6
Issue number5
StatePublished - May 2000
Externally publishedYes

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Dendritic Cells
Cell Differentiation
Neoplasms
Lung Neoplasms
Endothelial Growth Factors
Tumor Escape
Macrophage Colony-Stimulating Factor
Transforming Growth Factors
Granulocyte-Macrophage Colony-Stimulating Factor
Head and Neck Neoplasms
Interleukin-10
Vascular Endothelial Growth Factor A
Immune System
Interleukin-6
Breast
Lymph Nodes
Antibodies

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Almand, B., Resser, J. R., Lindman, B., Nadaf, S., Clark, J. I., Kwon, E. D., ... Gabrilovich, D. I. (2000). Clinical significance of defective dendritic cell differentiation in cancer. Clinical Cancer Research, 6(5), 1755-1766.

Clinical significance of defective dendritic cell differentiation in cancer. / Almand, Bond; Resser, John R.; Lindman, Brian; Nadaf, Sorena; Clark, Joseph I.; Kwon, Eugene D; Carbone, David P.; Gabrilovich, Dmitry I.

In: Clinical Cancer Research, Vol. 6, No. 5, 05.2000, p. 1755-1766.

Research output: Contribution to journalArticle

Almand, B, Resser, JR, Lindman, B, Nadaf, S, Clark, JI, Kwon, ED, Carbone, DP & Gabrilovich, DI 2000, 'Clinical significance of defective dendritic cell differentiation in cancer', Clinical Cancer Research, vol. 6, no. 5, pp. 1755-1766.
Almand B, Resser JR, Lindman B, Nadaf S, Clark JI, Kwon ED et al. Clinical significance of defective dendritic cell differentiation in cancer. Clinical Cancer Research. 2000 May;6(5):1755-1766.
Almand, Bond ; Resser, John R. ; Lindman, Brian ; Nadaf, Sorena ; Clark, Joseph I. ; Kwon, Eugene D ; Carbone, David P. ; Gabrilovich, Dmitry I. / Clinical significance of defective dendritic cell differentiation in cancer. In: Clinical Cancer Research. 2000 ; Vol. 6, No. 5. pp. 1755-1766.
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