Purpose: To examine the appearance and distribution of folate receptor β-expressing (FRβ+) macrophages in the pancreatic tumor microenvironment and their relationship to metastasis and prognosis in pancreatic cancer patients.
Methods: Tumor samples were obtained from 76 patients with pancreatic cancer who underwent curative resection. None of these patients had received any preoperative chemotherapy or radiotherapy. Both FRβ+ and tumor-infiltrating (CD68+) macrophages were examined in each tumor specimen by immunohistochemical and immunofluorescence staining using a newly developed anti-human FRβ monoclonal antibody and CD68 antibody. The appearance, distribution, expression of vascular endothelial growth factor (VEGF) on FRβ-expressing or CD68+ macrophages, and tumor microvessel density (MVD) were assessed. Log rank test and Cox proportional hazard regression were used to investigate the associations among CD68+ or FRβ+ macrophages, clinicopathologic factors, and overall survival.
Results: FRβ+ macrophages were prominent in the perivascular regions of the tumor-invasive front and a specific subset with VEGF expression in the CD68+ macrophages. A high number of FRβ+ macrophages showed a positive association with high MVD, a high incidence of hematogenous metastasis, and a poor prognosis in pancreatic cancer patients.
Conclusions: FRβ+ macrophages are a novel subset of tumor-associated macrophages in pancreatic cancer and may play an important role in the tumor microenvironment in association with systemic metastasis through the interaction with tumor cells and vessels. FRβ+ macrophages may be promising a targeting therapy for pancreatic cancer.