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


METHODS
We conducted a prospective trial in patients with high-risk (stage III B/C, IV), resected melanoma, with GM-CSF 125 microg/m(2)/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.


CONCLUSIONS
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.
Daud
Adil I
AI
H. Lee Moffitt Cancer Center, Tampa, FL, USA. adaud@medicine.ucsf.edu
Mirza
Noweeda
N
Lenox
Brianna
B
Andrews
Stephanie
S
Urbas
Patricia
P
Gao
Gui X
GX
Lee
Ji-Hyun
JH
Sondak
Vernon K
VK
Riker
Adam I
AI
Deconti
Ronald C
RC
Gabrilovich
Dmitry
D
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003713:Dendritic Cells / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008545:Melanoma / Q000097:blood / Q000188:drug therapy* / Q000473:pathology*; D008875:Middle Aged; D010641:Phenotype; D011446:Prospective Studies; D015996:Survival Rate; D016896:Treatment Outcome
D016178:Granulocyte-Macrophage Colony-Stimulating Factor