Circulating CD14+CD204+ Cells Predict Postoperative Recurrence in Non–Small-Cell Lung Cancer Patients

Abstract

The expression of CD204 on macrophages in the stroma of the primary tumor is reportedly correlated with an unfavorable prognosis for lung cancer. The purpose of this study is to investigate the correlation among the number of CD204 tumor-associated macrophages infiltrating the stroma of the primary tumor, the number of circulating CD14CD204 cells from the pulmonary vein (PV), and recurrence-free probability in non-small-cell lung cancer patients. Human mononuclear cells were isolated from the PV of resected lungs. We examined the expressions of CD14 and CD204 on these cells by flow cytometry. Immunohistochemical staining for CD204 was performed in the resected specimens. The number of CD14CD204 cells from the PV was found to be correlated with the number of CD204 tumor-associated macrophages identified in the stroma of the tumor. Significantly more cases with high levels of CD14CD204 cells from the PV were found to have developed early recurrences. CD14CD204 cells, which were polarized to the tumor-promoting phenotype cultured in lung cancer cell line-conditioned medium, facilitated the lung metastasis of cancer cells more effectively than CD14CD204 cells in our in vivo mouse model. In multivariate analysis, only the high number of CD14CD204 cells from the PV was found to be a statistically significant independent risk factor for early recurrence. Our results showed the possibility that circulating CD14CD204 cells contribute to the metastasis of cancer cells. The blockage of circulating CD14CD204 cells activity may prevent postoperative recurrence in resected non-small-cell lung cancer patients.