Abstract
BackgroundRegulatory T cells (Treg) suppress cytotoxic T cell anti-tumoral immune responses and thereby promote tumor progression. Prevention of intratumoral Treg accumulation by inhibition of their migration to the tumor microenvironment is a promising therapeutic strategy. The aim of this study was to identify the role of the two major Treg-attracting chemokines CCL1 and CCL22 in human breast cancer.MethodsOne hundred ninety-nine tissue samples of patients with invasive breast cancer were stained for CCL1 and CCL22 by immunohistochemistry. Chemokine expression and tumor infiltration by regulatory T cells, determined by expression of the transcription factor FoxP3, were quantified and their correlation to clinical features was statistically analyzed.ResultsBoth CCL1 and CCL22 were expressed in most breast cancer tissues. CCL1 was significantly over-expressed in invasive breast cancer as compared to normal breast tissue. CCL1, but surprisingly not CCL22, showed a significant correlation with the number of tumor-infiltrating FoxP3+ Treg (p< 0.001). High numbers of intratumoral CCL1 expressing cells were related to high grade tumors (G4) and a positive estrogen receptor (ER) status whereas high CCL22 expression was generally seen in lower grade tumors. The median survival of 88 patients with high intratumoral CCL1 expression was 37 months compared to 50 months for the 87 patients with low CCL1 levels, this trend was however not statistically significant.ConclusionsWe found a high expression of CCL1 in human breast cancer. CCL1 significantly correlated with the infiltration of immunosuppressive FoxP3+ Treg, that are known to negatively affect survival. Thus, CCL1 may serve as prognostic marker and novel therapeutic target in breast cancer.
Highlights
Regulatory T cells (Treg) suppress cytotoxic T cell anti-tumoral immune responses and thereby promote tumor progression
We found a significantly increased expression of CCL1 in breast cancer tissues, which was related to a higher infiltration of Treg
High expression of CCL1 in invasive breast cancer It is well established that high infiltration by Forkhead Box P3 (FoxP3)+ Treg has an adverse effect on prognosis in breast cancer [30]
Summary
Regulatory T cells (Treg) suppress cytotoxic T cell anti-tumoral immune responses and thereby promote tumor progression. Breast cancer is the most frequent cancer in women worldwide, currently affecting 12% of all women at one time in their life [1]. It is a heterogeneous disease including a wide range of biological behaviors and prognostic characteristics [2]. Regulatory T cells (Treg) are a subtype of immunosuppressive CD4+ T cells that inhibit the cytotoxic function of CD8+ T lymphocytes [9]. The physiological role of Treg is to protect the body from autoimmunity by suppressing self-reactive cells, including CD8+ cytotoxic T cells, B cells and natural killer cells (NK cells) [10, 11]
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