Association of Intra-tumoral Infiltrating Macrophages and Regulatory T Cells Is an Independent Prognostic Factor in Gastric Cancer after Radical Resection

Abstract

Macrophages (Mφ) and regulatory T cells (Tregs) are the major components of the inflammatory infiltrate in virtually all tumors. The objective of this study was to investigate the prognostic significance of Mφ and Tregs infiltration in advanced gastric cancer after radical resection. CD68(+) Mφ and FOXP3(+) Tregs were assessed by immunohistochemistry in tissues from 107 patients with surgically advanced gastric cancer. The microlocalization of Mφ and Tregs cells with respect to the development of gastric cancer were given special concern. Prognostic value of normal, peritumoral, and intratumoral Mφ and Tregs densities was evaluated by Kaplan-Meier analysis and Cox regression. The results showed that the presence of intratumoral CD68(+) Mφ was an independent prognostic factor for overall survival (OS) (P=0.02). Moreover, the combination of high numbers of intratumoral CD68(+) Mφ and FOXP3(+) Tregs was associated with improved survival (P=0.041). Five-year OS rate was only 27% for patients with low intratumoral Mφ and intratumoral Tregs compared with 62% for patients with high intratumoral Mφ and intratumoral Tregs. In addition, advanced intestinal-type gastric cancers were more likely to have fewer infiltrating Mφ than diffuse-type cancers (P=0.024). Association of intratumoral Mφ and Tregs is a promising independent predictor for survival in advanced gastric cancer. The results suggested that a combination of concomitant stimulation of intratumoral Mφ and Tregs may be an effective strategy for treatment of patients with advanced gastric cancer after radical resection.