Significance of the monocyte CCR2-CCL2 axis in triple-negative breast cancer

Abstract

Background

The monocyte CCR2-CCL2 axis appears to play a crucial role in the generation of tumor-associated macrophages (TAMs), which subsequently promotes tumor metastasis and resistance to therapy.

Aims

Our study assessed the monocyte CCR2-CCL2 axis in triple-negative breast cancer (TNBC) and its ability to predict tumor response to neoadjuvant chemotherapy (NAC).

Methods

The study included 42 female patients diagnosed with TNBC and eligible for NAC. Response to neoadjuvant chemotherapy was based on pathological complete response (pCR). Surface expression of CCR2 on monocytes was evaluated by flow cytometry. Circulating CCL2 was measured by Luminex X-Map technology.

Results

Increased monocyte CCR2 expression and higher circulating CCL2 levels were observed in the patients with TNBC. After dividing the patients according to their response to NAC, a significant difference in CCL2 levels was found only between patients who achieved pCR and those who did not. ROC curves showed that the optimum diagnostic cut-off value of CCL2 ≤89.61 pg/mL better discriminated patients with TNBC who achieved pCR better than the Ki-67 index. Univariate analysis demonstrated that circulating. CCL2 ≤89.61 pg/mL was significantly associated with pCR. However, this correlation lost statistical significance in the multivariate model.

Conclusions

Our study demonstrated the activation of the monocyte CCR2-CCL2 axis in TNBC for the first time. This activation occurs mainly in patients who do not respond to NAC. Circulating CCL2 levels ≤89.61 pg/mL were found to predict, to some extent, the achievement of pCR in patients with TNBC receiving NAC.