Phenotypic and functional analysis of dendritic cells and clinical outcome in patients with high-risk melanoma treated with adjuvant granulocyte macrophage colony-stimulating factor

Daud, Adil I., Mirza, Noweeda, Lenox, Brianna, Andrews, Stephanie, Urbas, Patricia, Gao, Gui X., Lee, Ji-Hyun, Sondak, Vernon K., Riker, Adam I., DeConti, Ronald C. and Gabrilovich, Dmitry (2008) Phenotypic and functional analysis of dendritic cells and clinical outcome in patients with high-risk melanoma treated with adjuvant granulocyte macrophage colony-stimulating factor. Journal of Clinical Oncology, 26 19: 3235-3241. doi:10.1200/JCO.2007.13.9048

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Author Daud, Adil I.
Mirza, Noweeda
Lenox, Brianna
Andrews, Stephanie
Urbas, Patricia
Gao, Gui X.
Lee, Ji-Hyun
Sondak, Vernon K.
Riker, Adam I.
DeConti, Ronald C.
Gabrilovich, Dmitry
Title Phenotypic and functional analysis of dendritic cells and clinical outcome in patients with high-risk melanoma treated with adjuvant granulocyte macrophage colony-stimulating factor
Journal name Journal of Clinical Oncology   Check publisher's open access policy
ISSN 0732-183X
Publication date 2008-07-01
Sub-type Article (original research)
DOI 10.1200/JCO.2007.13.9048
Open Access Status File (Publisher version)
Volume 26
Issue 19
Start page 3235
End page 3241
Total pages 7
Place of publication United States
Publisher American Society of Clinical Oncology
Language eng
Formatted abstract
Purpose:
Granulocyte macrophage colony-stimulating factor (GM-CSF) can induce differentiation of dendritic cells (DCs) in preclinical models. We hypothesized that GM-CSF-stimulated DC differentiation may result in clinical benefit in patients with high-risk melanoma.

Patients and Methods:

We conducted a prospective trial in patients with high-risk (stage III B/C, IV), resected melanoma, with GM-CSF 125 μg/m2/d administered for 14 days every 28 days. Patients underwent clinical restaging every four cycles, with DC analysis performed at baseline and at 2, 4, 8, and 12 weeks.

Results:

Of 42 patients enrolled, 39 were assessable for clinical outcome and DC analysis. Median overall survival was 65 months (95% CI, 43 to 67 months) and recurrence-free survival was 5.6 months (95% CI, 3 to 11 months). GM-CSF treatment caused an increase in mature DCs, first identified after 2 weeks of treatment, normalizing by 4 weeks. Patients with decreased DCs at baseline had significant increases in DC number and function compared with those with "normal" parameters at baseline. No change was observed in the number of myeloid-derived suppressor cells (MDSCs). Early recurrence (< 90 days) correlated with a decreased effect of GM-CSF on host DCs, compared with late or no (evidence of) recurrence.

Conclusion:
GM-CSF treatment was associated with a transient increase in mature DCs, but not MDSCs. Greater increase of DCs was associated with remission or delayed recurrence. The prolonged overall survival observed warrants further exploration.
Keyword Myeloid Suppressor-Cells
Factor Gm-Csf
Cancer-Patients
Metastatic Melanoma
Immune-Response
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collections: ERA 2012 Admin Only
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