Purpose: Tumor-associated macrophages (TAMs) can promote or dampen breast cancer progression, depending on phenotypic changes within the cancer microenvironment. Two contrasting activation states were described in the literature: the M1 anti-tumoral and M2 pro-tumoral subtype of TAMs. In clinical observation, we analyzed the TRAcP expression in breast cancer TAM and correlated to patient's chemotherapy responses and survival. In animal models, we aim to investigate the tumor-promoting or inhibiting properties among tartrate-resistant acid phosphatase (TRAcP) expressed TAMs.

Methods: TRAcP expression, T lymphocytes, and other macrophage relevant markers were determined by immunohistochemical staining in the human breast cancer tissue from the patients before neoadjuvant chemotherapy. The expression of TRAcP within the TAMs were calculated and correlated to the patient's chemotherapy responsiveness and outcome. The polarized M1/M2 macrophages and breast cancer hematogenous metastasis were created in the animal model. Activated macrophages from TRAcP+/+ or TRAcP−/− mice were injected with JC (Balb/c breast cancer) cells in the metastatic model.

Results: The presence of Foxp3+ regulatory T cell (Treg) correlates to the tumor proliferation (Ki-67 and Her2 expression) and higher Foxp3+ Treg prevalence and tumor Ki-67 expression inferred poorer chemotherapy response. TRAcP staining within the CD68+ macrophages were observed with better chemotherapy response. In animal model, M2 polarized macrophages have higher TRAcP expression, promote breast cancer metastasis, and attract Treg infiltrating in tumor, consistent with the clinical observation.

Conclusion: TRAcP-expressing TAMs, representing M2-polarized macrophage, demonstrat local tumor-promoting and immune-suppressive effects, and chemotherapy resistance. TRAcP expression within TAM can be a potential prognostic marker for breast cancer.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-04-07.

This abstract was not presented at the conference.