Heng Zhang1, Xuefei Wang1, Zhenbin Shen1, Jiejie Xu2,3, Jing Qin4, Yihong Sun5. 1. Department of General Surgery, Zhongshan Hospital, Shanghai Medical College of Fudan University, 180 Feng Lin Road, Shanghai, 200032, China. 2. Key Laboratory of Glycoconjugate Research, Ministry of Health, Shanghai, China. jjxufdu@fudan.edu.cn. 3. Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shanghai Medical College of Fudan University, 138 Yi Xue Yuan Road, PO Box 103, Shanghai, 200032, China. jjxufdu@fudan.edu.cn. 4. Department of General Surgery, Zhongshan Hospital, Shanghai Medical College of Fudan University, 180 Feng Lin Road, Shanghai, 200032, China. qin.jing@zs-hospital.sh.cn. 5. Department of General Surgery, Zhongshan Hospital, Shanghai Medical College of Fudan University, 180 Feng Lin Road, Shanghai, 200032, China. sun.yihong@zs-hospital.sh.cn.
Abstract
BACKGROUND: Tumor-associated macrophages (TAMs), the most predominant tumor-infiltrating immune cells, are emerging prognostic factors and therapeutic targets for personalized therapy against malignant neoplasms. We aimed to evaluate the prognostic significance of diametrically polarized TAMs in gastric cancer and generate a predictive nomogram to refine a risk stratification system. METHODS: We evaluated polarized functional status of infiltrated TAMs by immunohistochemical staining of CD68, CD11c, and CD206 in 180 consecutive gastric cancer patients from Zhongshan Hospital, Shanghai, China. Prognostic values were assessed in these patients. We created a predictive nomogram by integrating polarized TAMs with the TNM staging system for overall survival of gastric cancer patients. RESULTS: CD68(+) TAMs display polarized programs comprising CD11c(+) proinflammatory macrophages (M1) and CD206(+) immunosuppressive macrophages (M2) that configure versatile infiltration files in gastric cancer. CD11c(+) TAMs negatively correlated with lymph node metastasis (p = 0.012), whereas CD206(+) TAMs correlated with the Lauren classification (p = 0.031). No prognostic difference was observed for overall survival for CD68 density (high vs low, p = 0.1031), whereas high versus low CD11c density (p < 0.0001) and low vs high CD206 density (p = 0.0105) indicate better overall survival. Multivariate Cox regression analysis identified CD11c and CD206 as independent prognostic factors (p < 0.001 and p = 0.030, respectively), which could be integrated with the TNM staging system to generate a predictive nomogram for patient outcomes. CONCLUSION: Infiltration of polarized TAMs, a novel identified independent prognostic factor, could be combined with the TNM stage to refine a risk stratification system and better stratify patients with different prognosis. Tipping TAMs to an antitumoral phenotype might be a promising therapeutic target for postoperative treatment.
BACKGROUND:Tumor-associated macrophages (TAMs), the most predominant tumor-infiltrating immune cells, are emerging prognostic factors and therapeutic targets for personalized therapy against malignant neoplasms. We aimed to evaluate the prognostic significance of diametrically polarized TAMs in gastric cancer and generate a predictive nomogram to refine a risk stratification system. METHODS: We evaluated polarized functional status of infiltrated TAMs by immunohistochemical staining of CD68, CD11c, and CD206 in 180 consecutive gastric cancerpatients from Zhongshan Hospital, Shanghai, China. Prognostic values were assessed in these patients. We created a predictive nomogram by integrating polarized TAMs with the TNM staging system for overall survival of gastric cancerpatients. RESULTS:CD68(+) TAMs display polarized programs comprising CD11c(+) proinflammatory macrophages (M1) and CD206(+) immunosuppressive macrophages (M2) that configure versatile infiltration files in gastric cancer. CD11c(+) TAMs negatively correlated with lymph node metastasis (p = 0.012), whereas CD206(+) TAMs correlated with the Lauren classification (p = 0.031). No prognostic difference was observed for overall survival for CD68 density (high vs low, p = 0.1031), whereas high versus low CD11c density (p < 0.0001) and low vs high CD206 density (p = 0.0105) indicate better overall survival. Multivariate Cox regression analysis identified CD11c and CD206 as independent prognostic factors (p < 0.001 and p = 0.030, respectively), which could be integrated with the TNM staging system to generate a predictive nomogram for patient outcomes. CONCLUSION: Infiltration of polarized TAMs, a novel identified independent prognostic factor, could be combined with the TNM stage to refine a risk stratification system and better stratify patients with different prognosis. Tipping TAMs to an antitumoral phenotype might be a promising therapeutic target for postoperative treatment.
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