Abstract
ObjectiveComprehensive studies have investigated the prognostic and clinicopathological value of tumor-associated macrophages (TAMs) in gastric cancer patients, yet results remain controversial. Therefore, we performed a meta-analysis to clarify this issue.MethodsPubMed, Embase, and the Cochrane Library databases were searched to identify eligible studies. We extracted hazard ratios (HRs) and odds ratios (ORs) with their corresponding 95% confidence intervals (95% CIs) to estimate the effect sizes. In addition, subgroup analysis and sensitivity analysis were also conducted.ResultsA total of 19 studies involving 2242 patients were included. High generalised TAMs density was significantly associated with poor overall survival (OS) (HR 1.49, 95% CI 1.15–1.95). Subgroup analysis revealed that CD68+ TAMs had no significant effect on OS (HR 1.38, 95% CI 1.00–1.91). High M1 TAMs density was correlated with better OS (HR 0.45, 95% CI 0.32–0.65). By contrast, high density of M2 TAMs was correlated with a poor prognosis for OS (HR 1.48, 95% CI 1.25–1.75). Furthermore, high M2 TAMs density was correlated with larger tumor size, diffuse Lauren type, poor histologic differentiation, deeper tumor invasion, lymph node metastasis, and advanced TNM stage.ConclusionsOverall, this meta-analysis reveal that although CD68+ TAMs infiltration has the neutral prognostic effects on OS, the M1/M2 polarization of TAMs are predicative factor of prognosis in gastric cancer patients.
Highlights
Gastric cancer represents the fifth most common malignancy and the third leading cause of cancer death in the world [1]
M2 macrophages are mainly activated by Th2 cytokines, which participate in the antiinflammatory response, tissue remodeling, angiogenesis and tumor cell activation [5,6,7,8]
We examined the effect of CD68+, M1 and M2 Tumor-associated macrophages (TAMs) on the overall survival of patients with gastric cancer
Summary
Gastric cancer represents the fifth most common malignancy and the third leading cause of cancer death in the world [1]. Despite recent advances in the diagnosis and medical treatment of gastric cancer, patient survival remains poor, especially for those in the advanced stages of the disease [2]. Tumor-associated macrophages (TAMs), as fundamental components of the inflammatory microenvironment of tumors, originate from circulating monocytes and are recruited to the tumor site [4, 5]. Different microenvironments can lead to two different polarizations of TAMs: the classically activated type M1 phenotype and the alternatively activated M2 phenotype. M2 macrophages are mainly activated by Th2 cytokines (e.g., interleukin 4, interleukin 13), which participate in the antiinflammatory response, tissue remodeling, angiogenesis and tumor cell activation [5,6,7,8]
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