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Erschienen in: Gastric Cancer 4/2015

01.10.2015 | Original Article

Infiltration of diametrically polarized macrophages predicts overall survival of patients with gastric cancer after surgical resection

verfasst von: Heng Zhang, Xuefei Wang, Zhenbin Shen, Jiejie Xu, Jing Qin, Yihong Sun

Erschienen in: Gastric Cancer | Ausgabe 4/2015

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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.
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Metadaten
Titel
Infiltration of diametrically polarized macrophages predicts overall survival of patients with gastric cancer after surgical resection
verfasst von
Heng Zhang
Xuefei Wang
Zhenbin Shen
Jiejie Xu
Jing Qin
Yihong Sun
Publikationsdatum
01.10.2015
Verlag
Springer Japan
Erschienen in
Gastric Cancer / Ausgabe 4/2015
Print ISSN: 1436-3291
Elektronische ISSN: 1436-3305
DOI
https://doi.org/10.1007/s10120-014-0422-7

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