Abstract
PurposeAs mayor biomarkers in tumor microenvironment (TME), tumor associated macrophages (TAMs) of gastric cancer (GC) still needs further studies in terms of the number and distribution pattern.MethodsHerein, tissue microarrays (TMA) incorporating 494 GC surgical samples in duplicate were stained for TAMs infiltration analysis. TAMs number was counted according to the locations, including infiltrating macrophages in cancer nest (MC), in invasive front (MF) and in stroma (MS). Correlations between TAMs number, distribution pattern and clinic-pathological features and survival analyses were performed.ResultsInfiltrating macrophages number in GC tissues was much higher than that in peritumoral tissues. TAMs number was not significantly correlated with the overall survival (OS). TAMs distribution pattern could be categorized into MC or MF/MS dominant pattern, and correlated with histological grade (P =0.001). The median OS of MF/MS dominant pattern (22.1, 95%CI: 23.5-28.9) was significantly shorter than that of MC dominant pattern (25.6, 95%CI: 28.5-35.6) (P =0.002). By receiver operating characteristic curve (ROC) analysis, the predictive value of TAMs distribution pattern was superior to histological grade and pM stage, but inferior to pN and TNM stage.ConclusionsTAMs distribution pattern could be an independent prognostic factor for the OS of GC patients, and patients with MF/MS dominant pattern had worse outcomes.
Highlights
Tumor microenvironment (TME) plays an important role in cancer progression and metastasis [1, 2]
Studies in gastric cancer (GC) have shown that higher number of Tumor associated macrophages (TAMs) is associated with worse prognosis [7, 8]
Some studies have suggested that GC TAMs in different locations play different roles in relation to angiogenesis, stromal reaction, and prognosis [18]. These results indicate that TAMs number and distributions are crucial factors to impact the coevolution between cancer cells and TAMs
Summary
Tumor microenvironment (TME) plays an important role in cancer progression and metastasis [1, 2]. Tumor associated macrophages (TAMs), the most abundant immune-related stromal cells [4], act as key orchestrators in TME, by directly attacking cancer cells, or promoting cancer progression by suppressing antitumor immunity, or inducing angiogenesis [5]. It becomes controversial that TAMs emerge as significant but opposite predictors of survival for GC [10, 11]. These conflicting results could be due to the fact that most studies pay attention to the ratios of TAMs with different phenotypic features [12, 13], or ignorance of TAMs distributions by focusing on the number
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