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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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).
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.
KeywordsDendritic cell vaccine chemokine cytoarray melanoma ELISA
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.
- 12.Choi D, Perrin M, Hoffmann S, Chang AE, Ratanatharathorn V, Uberti J, et al. Dendritic cell-based vaccines in the setting of peripheral blood stem cell transplantation: CD34 + cell-depleted mobilized peripheral blood can serve as a source of potent dendritic cells. Clin Cancer Res. 1998;4:2709–16.PubMedGoogle Scholar
- 17.Dillman RO, Beutel LD, Barth NM, de Leon C, O’Connor AA, DePriest C, et al. Irradiated cells from autologous tumor cell lines as patient-specific vaccine therapy in 125 patients with metastatic cancer: induction of delayed-type hypersensitivity to autologous tumor is associated with improved survival. Cancer Biother Radiopharm. 2002;17:51–66. doi: 10.1089/10849780252824073.PubMedCrossRefGoogle Scholar
- 18.Shapiro SS, Wilk M. An analysis of variance test for normality (complete samples). Biometrika. 1965;52:591–611.Google Scholar
- 24.Lebre MC, Burwell T, Vieira PL, Lora J, Coyle AJ, Kapsenberg ML, et al. Differential expression of inflammatory chemokines by Th1- and Th2-cell promoting dendritic cells: a role for different mature dendritic cell populations in attracting appropriate effector cells to peripheral sites of inflammation. Immunol Cell Biol. 2005;83:525–35. doi: 10.1111/j.1440-1711.2005.01365.x.PubMedCrossRefGoogle Scholar
- 26.Kanagawa N, Niwa M, Hatanaka Y, Tani Y, Nakagawa S, Fujita T, et al. CC-chemokine ligand 17 gene therapy induces tumor regression through augmentation of tumor-infiltrating immune cells in a murine model of preexisting CT26 colon carcinoma. Int J Cancer. 2007;121:2013–22. doi: 10.1002/ijc.22908.PubMedCrossRefGoogle Scholar
- 27.Okada N, Sasaki A, Niwa M, Okada Y, Hatanaka Y, Tani Y, et al. Tumor suppressive efficacy through augmentation of tumor-infiltrating immune cells by intratumoral injection of chemokine-expressing adenoviral vector. Cancer Gene Ther. 2006;13:393–405. doi: 10.1038/sj.cgt.7700903.PubMedCrossRefGoogle Scholar
- 28.Nakazaki Y, Hase H, Inoue H, Beppu Y, Meng XK, Sakaguchi G, et al. Serial analysis of gene expression in progressing and regressing mouse tumors implicates the involvement of RANTES and TARC in antitumor immune responses. Mol Ther. 2006;14:599–606. doi: 10.1016/j.ymthe.2006.04.014.PubMedCrossRefGoogle Scholar
- 30.Imai T, Nagira M, Takagi S, Kakizaki M, Nishimura M, Wang J, et al. Selective recruitment of CCR4-bearing Th2 cells toward antigen-presenting cells by the CC chemokines thymus and activation-regulated chemokine and macrophage-derived chemokine. Int Immunol. 1999;11:81–8. doi: 10.1093/intimm/11.1.81.PubMedCrossRefGoogle Scholar