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Cancer Sci. 2019 Nov 14. doi: 10.1111/cas.14234. [Epub ahead of print]

Significant association between high serum CCL5 levels and better disease-free survival of patients with early breast cancer.

Author information

1
Department of Surgery, Division of Breast and Endocrine Surgery, Hyogo College of Medicine, Mukogawa-cho 1-1, Nishinomiya, Hyogo, 663-8501, Japan.
2
Osaka Ryokuryo High School, Kasugaoka 3-8-1, Fujiidera, Osaka, 583-8558, Japan.
3
Department of Surgery, National Hospital Organization Osaka National Hospital, Hoenzaka 2-1-14, Chuo-ku, Osaka, 540-0006, Japan.
4
Biofunctional Synthetic Chemistry Laboratory, RIKEN Cluster for Pioneering Research, Hirosawa 2-1, Wako, Saitama, 351-0198, Japan.
5
Department of Surgical Pathology, Hyogo College of Medicine, Mukogawa-cho 1-1, Nishinomiya, Hyogo, 663-8501, Japan.
6
Division of Genome Medicine, Institute for Genome Research, Tokushima University, Kuramoto-cho 3-18-15, Tokushima, 770-8503, Japan.
7
Laboratory of Tumor Immunology and Cell Therapy, Hyogo College of Medicine, Mukogawa-cho 1-1, Nishinomiya, Hyogo, 663-8501, Japan.

Abstract

Analysis of anti-cancer immunity aids in assessing the prognosis of patients with breast cancer. From 250 operated breast cancers, we focused on serum levels of C-C motif chemokine ligand 5 (CCL5), which is involved in cancer immune reactions. Serum levels of CCL5 were measured using a cytometric bead-based immunoassay kit and CCL5 expression in cancer cells was determined using immunohistochemical staining. In addition, mRNA in cancer and stromal cells was analyzed by microdissection and comparison with the public dataset. Disease-free survival (DFS) of patients with high CCL5 levels (cut-off, 13.87 ng/mL; n = 192) was significantly better than those with low CCL5 levels (n = 58; hazard ratio, 0.20; 95% confidence interval, 0.10-0.39; p < 0.0001). An improved overall survival was observed in patients with high CCL5 levels compared to those with low CCL5 levels (p = 0.024). On the contrary, high immunohistochemical expression of CCL5 in cancer cells was significantly associated with decreased DFS. Since serum CCL5 levels did not correlate with CCL5 expression in cancer cells and the relative expression of mRNA CCL5 was elevated in stromal cells in relation to cancer cells, serum CCL5 may be derived not from cancer cells, but from stromal cells. CCL5 expression in serum but not in cancer cells may contribute to improved patient prognosis mediating through not only immune reaction, but through other mechanisms. Determination of circulating CCL5 levels may be useful for predicting patient prognosis.

KEYWORDS:

CCL5; breast cancer; cytokine; immunity; prognosis

PMID:
31724785
DOI:
10.1111/cas.14234
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