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Dynamics of chemokine, cytokine, and growth factor serum levels in BRAF-mutant melanoma patients during BRAF inhibitor treatment.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2014 Mar 01; Vol. 192 (5), pp. 2505-13. Date of Electronic Publication: 2014 Jan 31. - Publication Year :
- 2014
-
Abstract
- The purpose of this study is to profile the changes in the serum levels of a range of chemokines, cytokines, and growth and angiogenic factors in MAPK inhibitor-treated metastatic melanoma patients and to correlate these changes with clinical outcome and changes in melanoma tissue biopsies taken from the same patients. Forty-two chemokine, cytokine, angiogenic, and growth factors were measured in the sera of 20 BRAF inhibitor-treated and four combination BRAF and MEK inhibitor-treated metastatic melanoma patients using a multiplex chemokine assay. The changes were correlated with Ki-67 and CD8(+) tumor-infiltrating lymphocytes in the tumor biopsies taken at the same time points, as well as clinical outcome, including response rate, progression-free survival, and overall survival. Serum levels of IFN-γ, CCL4, and TNF-α were significantly increased, whereas CXCL8 significantly decreased from pretreatment (PRE) to early during treatment (EDT) serum samples. The decrease in serum CXCL8 levels from PRE to EDT significantly correlated with decreases in markers of melanoma proliferation (Ki-67) and increases in cytotoxic tumor-infiltrating T cells in corresponding tumor biopsies. In addition, a greater fold reduction in CXCL8 serum levels from PRE to EDT serum samples was associated with decreased overall survival. These results suggest that BRAF inhibition causes decreased CXCL8 secretion from melanoma cells and induce an immune response against the tumor associated with increased IFN-γ, CCL4, and TNF-α. Further studies are needed to determine if CXCL8 is predictive of response and to confirm the functions of these chemokine and cytokine in BRAF-mutant melanoma under BRAF inhibition.
- Subjects :
- Adult
Aged
CD8-Positive T-Lymphocytes immunology
CD8-Positive T-Lymphocytes pathology
Cytokines genetics
Female
Humans
Ki-67 Antigen genetics
Ki-67 Antigen immunology
Male
Melanoma drug therapy
Melanoma genetics
Melanoma pathology
Middle Aged
Proto-Oncogene Proteins B-raf genetics
Proto-Oncogene Proteins B-raf immunology
Cytokines immunology
Melanoma immunology
Protein Kinase Inhibitors administration & dosage
Proto-Oncogene Proteins B-raf antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 192
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 24489105
- Full Text :
- https://doi.org/10.4049/jimmunol.1302616