Increases in serum TARC/CCL17 levels are associated with progression-free survival in advanced melanoma patients in response to dendritic cell-based immunotherapy.
BACKGROUND
Changes in the levels of serum cytokines and growth factors are associated with response to therapy. We examined cytokine, chemokine, and growth factor levels in serum collected from normal volunteers or metastatic melanoma patients receiving dendritic cell-based immunotherapy.


METHODS
Using an array for 42 cytokines, chemokines, or growth factors, sera from normal controls and metastatic melanoma patients at baseline and week 4 were analyzed for qualitative changes. Quantitative determination of the levels of the chemokine thymus and activation-regulated chemokine (TARC/CCL17) was determined by enzyme-linked immunosorbent assay (ELISA).


RESULTS
Significant qualitative differences were noted in serum cytokine, chemokine, and growth factor levels of metastatic melanoma patients versus the normal controls at baseline. The results also demonstrated a significant decrease in the level of angiogenin (P = 0.026) and a significant increase in TARC/CCLl7 (P = 0.008) from week 0 to week 4 which was associated with improved overall survival (P = 0.059). Higher TARC/CCL17 levels were observed by ELISA at week 4 and a log-rank comparison revealed a significant association between high serum TARC/CCL17 levels at week 4 and progression-free survival (P = 0.005). Receiver-operator characteristic analysis revealed that week 4 serum TARC/CCL17 levels were predictive of progression-free and overall survival, indicating that serum TARC/CCL17 might be of predictive value of response to dendritic cell-based anti-melanoma immunotherapy.
Cell Biology Laboratory, Hoag Cancer Center, Newport Beach, CA 92663, USA. Andrew.Cornforth@hoaghospital.org
Andrew N
AN
Cornforth
Gregory J
GJ
Lee
Abner W
AW
Fowler
Denysha J
DJ
Carbonell
Robert O
RO
Dillman
D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D054414:Chemokine CCL17 / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016219:Immunotherapy, Adoptive; D008297:Male; D008545:Melanoma / Q000097:blood / Q000175:diagnosis / Q000276:immunology* / Q000401:mortality / Q000628:therapy; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D012259:Ribonuclease, Pancreatic / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics
D015415:Biomarkers; C106230:CCL17 protein, human; D054414:Chemokine CCL17; C046366:angiogenin; D012259:Ribonuclease, Pancreatic