Impact of the CCR5 gene polymorphism on the survival of metastatic melanoma patients receiving immunotherapy.
OBJECTIVE
Chemokines influence both tumor progression and anti-tumor immune response. A 32-bp-deletion polymorphism in the chemokine receptor 5 gene (CCR5Delta32) has been shown to result in a non-functional protein. This study was aimed at evaluating the potential impact of this gene polymorphism on disease progression and treatment outcome in patients with melanoma.


METHODS
CCR5 genotyping was performed by PCR on DNA extracted from serum samples of 782 cutaneous melanoma patients with known disease history and long-term clinical follow-up. Genotypes were correlated with patient survival and types of treatment.


RESULTS
Of 782 melanoma patients, 90 (11.5%) were heterozygous and 12 (1.5%) were homozygous for CCR5Delta32. Analyzing the complete cohort, the disease-specific survival from date of primary diagnosis was not influenced by CCR5 status. Similarly, no significant impact could be detected on the treatment outcome of stage III patients. In 139 stage IV patients receiving immunotherapy, CCR5Delta32 was associated with a decreased survival compared to patients not carrying the deletion (median 12.5 vs. 20.3 months, P = 0.029). Multivariate analysis revealed the CCR5 genotype as an independent factor impacting disease-specific survival in this patient population (P = 0.002), followed by gender (P = 0.019) and pathological classification of the primary (pT; P = 0.022).


CONCLUSIONS
The presence of the CCR5Delta32 polymorphism in patients with stage IV melanoma results in a decreased survival following immunotherapy and may help to select patients less likely to benefit from this type of treatment.
Ugurel
Selma
S
Department of Dermatology, Julius-Maximilians University, Würzburg, Germany.
Schrama
David
D
Keller
Gunhild
G
Schadendorf
Dirk
D
Bröcker
Eva-Bettina
EB
Houben
Roland
R
Zapatka
Marc
M
Fink
Wolfram
W
Kaufman
Howard L
HL
Becker
Jürgen C
JC
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D005260:Female; D006801:Humans; D007167:Immunotherapy; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000401:mortality* / Q000628:therapy; D008875:Middle Aged; D011110:Polymorphism, Genetic; D019713:Receptors, CCR5 / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000628:therapy; D016896:Treatment Outcome
D019713:Receptors, CCR5