(c) Survival curves of CD8+high/CD163+high(n = 52) vs . In addition , the density of CD163+ TAMs correlated with tumor infiltrating lymphocytes (TILs). Our results indicate that the high density of CD163+ TAMs is an independent prognostic marker heralding prolonged disease-free survival and that the prognostic implication of CD163+ TAMs might be determined by the proportional balance of TAMs and TILs in MSI-high gastric cancers. == Introduction == Gastric cancer (GC) is estimated to be the fifth most common malignancy in the world and is the third most common cause of death in both male and female individuals [1]. GC is a heterogeneous disease in terms of mechanisms of molecular carcinogenesis, and microsatellite instability (MSI) accounts for 10% of GCs Galactose 1-phosphate [2, 3]. MSI is caused by genetic or epigenetic alterations of mismatch repair (MMR) genes and consequent alterations in the number of repeat nucleotides in coding or non-coding regions of the targeted genes. Compared with the MSI-low (MSI-L) or MS-stable (MSS) phenotype, MSI-high (MSI-H) GCs are characterized by some distinct clinicopathologic features, including more common GCs of intestinal type according to the Lauren classification, less frequent lymph node metastasis, and better prognosis [3]. At the same time, as a consequence of DNA mismatch repair deficiency, MSI-H GCs express many immunogenic antigens which lead to a high density of tumor infiltrating cytotoxic or regulatory T cells in the tumor stroma or tumor cells CDKN2D themselves [4, 5]. Consistent with the finding of tumor infiltrating lymphocytes (TILs), significantly enhanced numbers of tumor-associated macrophages (TAMs) have also been observed in MSI-H tumors compared with the MSS or MSI-L phenotype [6]. The tumor microenvironment plays a crucial role in many malignant tumors and involves several factors, including immune cells, fibroblasts, blood vessels, extracellular matrix, Galactose 1-phosphate and soluble factors. Among them, macrophages are thought to be the most abundant immune populations. The major functions and characteristics of TAMs have been previously studied by many researchers. In general, TAMs release numerous factors such as cytokines, chemokines and growth factors that influence the behaviors of tumor cells. Monocytes are considered to have functional and phenotypic plasticity that enables them to differentiate into two polarization statesM1 and M2 macrophagesdepending on the cytokine milieu in the tumor microenvironment [7]. Classically activated (M1) macrophages are induced by T helper type 1-like cytokines such as interferon- and microbial stimuli such as lipopolysaccharides and produce pro-inflammatory cytokines, chemokines and reactive nitrogen/oxygen intermediates. Thus, these cells are involved in anti-microbial and tumoricidal activity. In contrast, alternatively activated (M2) macrophages are induced by T helper type 2 cytokines including interleukin-4 (IL-4), IL-10 and IL-13 and show immunoregulatory, anti-inflammatory and tumor-promoting activity. In general, TAMs are considered to resemble the M2 phenotype more than the M1 phenotype [8]. Therefore , TAMs are thought to be associated with poor survival of cancer patients by promoting invasion, metastasis, angiogenesis and lymphangiogenesis. In fact , TAMs have been related to decreased survival in many solid tumors (e. g., ovary [9], melanoma [10], lung [11, 12], endometrium [13], breast [14, 15] and kidney [16, 17]) but not all (e. g., GCs, colorectal cancers (CRCs)). Several studies in GCs and CRCs have demonstrated better prognosis in patients with a high density of TAMs [1821], which indicates that the functional role of TAMs could be different depending on type of tissue and cancer. Because the molecular subtypes of GCs differ with regard to their clinicopathological features, including prognosis, Galactose 1-phosphate in order to clarify the role of TAMs on the survival outcome in GCs, it is important to minimize the effect of confounding factors associated with prognosis and increase the study groups homogeneity. MSI-H GCs are thought to provide an adequate platform to test whether TAMs are associated with good or poor survival. Thus, in the present study, a series of patients with MSI-H GCs was analyzed with regard to the.