Shunki Hirayama1, Genichiro Ishii2, Kanji Nagai3, Shotaro Ono4, Motohiro Kojima5, Chisako Yamauchi5, Keiju Aokage3, Tomoyuki Hishida3, Junji Yoshida3, Kenji Suzuki6, Atsushi Ochiai7. 1. Department of Pathology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan; Department of Thoracic Oncology, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan; Department of General Thoracic Surgery, Juntendo University School of Medicine, Tokyo, Japan. 2. Department of Pathology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan. Electronic address: gishii@east.ncc.go.jp. 3. Department of Thoracic Oncology, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan. 4. Department of Pathology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan; Department of Thoracic Oncology, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan. 5. Department of Pathology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan. 6. Department of General Thoracic Surgery, Juntendo University School of Medicine, Tokyo, Japan. 7. Department of Pathology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan. Electronic address: aochiai@east.ncc.go.jp.
Abstract
INTRODUCTION: Tumor-associated macrophages (TAMs) are recruited into cancer-induced stroma and produce a specific microenvironment for cancer progression. CD204 (+) TAMs are reportedly related to tumor progression and clinical outcome in some tumors. The aim of this study was to clarify the correlation between CD204 (+) TAMs and the clinicopathological features of lung squamous cell carcinoma. METHODS: We investigated the relationships between the numbers of CD204 (+) TAMs and clinicopathological factors, microvessel density, and the numbers of Foxp3 (+) lymphocytes in 208 consecutively resected cases. We also examined the relationships between the numbers of CD204 (+) TAMs and the expression levels of cytokines involved in the migration and differentiation of CD204 (+) TAMs. RESULTS: A high number of CD204 (+) TAMs in the stroma was significantly correlated with an advanced p-stage, T factor, N factor, and the presence of vascular and pleural invasion. A high number of CD204 (+) TAMs in the stroma was also a significant prognostic factor for all p-stages and p-stage I. Moreover, the numbers of CD204 (+) TAMs were correlated with the microvessel density and the numbers of Foxp3 (+) lymphocytes. A high number of CD204 (+) TAMs was strongly correlated with the tissue expression level of monocyte chemoattractant protein-1. CD204 (+) TAMs were shown to be significant independent prognostic factors in a multivariate analysis. CONCLUSIONS: CD204 (+) TAMs were an independent prognostic factor in lung squamous cell carcinoma. CD204 (+) TAMs, along with other tumor-promoting stromal cells such as regulatory T cells and endothelial cells, may create tumor-promoting microenvironments.
INTRODUCTION:Tumor-associated macrophages (TAMs) are recruited into cancer-induced stroma and produce a specific microenvironment for cancer progression. CD204 (+) TAMs are reportedly related to tumor progression and clinical outcome in some tumors. The aim of this study was to clarify the correlation between CD204 (+) TAMs and the clinicopathological features of lung squamous cell carcinoma. METHODS: We investigated the relationships between the numbers of CD204 (+) TAMs and clinicopathological factors, microvessel density, and the numbers of Foxp3 (+) lymphocytes in 208 consecutively resected cases. We also examined the relationships between the numbers of CD204 (+) TAMs and the expression levels of cytokines involved in the migration and differentiation of CD204 (+) TAMs. RESULTS: A high number of CD204 (+) TAMs in the stroma was significantly correlated with an advanced p-stage, T factor, N factor, and the presence of vascular and pleural invasion. A high number of CD204 (+) TAMs in the stroma was also a significant prognostic factor for all p-stages and p-stage I. Moreover, the numbers of CD204 (+) TAMs were correlated with the microvessel density and the numbers of Foxp3 (+) lymphocytes. A high number of CD204 (+) TAMs was strongly correlated with the tissue expression level of monocyte chemoattractant protein-1. CD204 (+) TAMs were shown to be significant independent prognostic factors in a multivariate analysis. CONCLUSIONS:CD204 (+) TAMs were an independent prognostic factor in lung squamous cell carcinoma. CD204 (+) TAMs, along with other tumor-promoting stromal cells such as regulatory T cells and endothelial cells, may create tumor-promoting microenvironments.