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Increases in Serum TARC/CCL17 Levels Are Associated with Progression-Free Survival in Advanced Melanoma Patients in Response to Dendritic Cell-Based Immunotherapy

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Abstract

Introduction

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.

Materials and 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.

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Acknowledgments

We would like to acknowledge Sarah Tillman and Andrea Beatty for their assistance in generating the tumor and dendritic cell lines, William McRorie for his assistance in the TARC/CCL17 ELISA, and Micheal Farr for his contribution to the cytoarray work. Acknowledgement should also go to Dr. Senthamil Selvan for his input in writing this manuscript. Funding for this work was provided by the Hoag Hospital Foundation.

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Authors and Affiliations

  1. Cell Biology Laboratory, Hoag Cancer Center, 1 Hoag Drive Bldg 41, Newport Beach, CA, 92663, USA

    Andrew N. Cornforth, Gregory J. Lee, Abner W. Fowler, Denysha J. Carbonell & Robert O. Dillman

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  1. Andrew N. Cornforth
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  2. Gregory J. Lee
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  3. Abner W. Fowler
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Correspondence to Andrew N. Cornforth.

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Cornforth, A.N., Lee, G.J., Fowler, A.W. et al. Increases in Serum TARC/CCL17 Levels Are Associated with Progression-Free Survival in Advanced Melanoma Patients in Response to Dendritic Cell-Based Immunotherapy. J Clin Immunol 29, 657–664 (2009). https://doi.org/10.1007/s10875-009-9299-3

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  • DOI: https://doi.org/10.1007/s10875-009-9299-3

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