IL-10 is associated with tumor malignancy via immune escape. ATA haplotype. This may be associated with the observation that the number of tumor-infiltrating lymphocytes was decreased in the tumors with higher levels of IL-10. Consistently, T cells from the peripheral blood of the patients with non-ATA haplotype were more susceptible to apoptosis and less cytotoxic to tumor cells, compared to those from the patients with ATA haplotype. The results suggest that IL-10 can promote tumor malignancy via promoting T cell apoptosis and tumor cell survival, and IL-10 haplotype evaluated by PCR-RFLP or direct sequencing may be used to predict survival and relapse in resected NSCLC, helping clinicians to make appropriate decisions on treatment of the patients. Introduction Interleukin-10 (IL-10), an important immunoinhibitory cytokine, is usually part of a balanced network of cytokines [1]C[5]. The IL-10 cytokine is usually produced by several cells including normal and neoplastic B cells, stimulated monocytes, macrophages, and a subset of T cells [1]C[4]. Many case-control studies have indicated an association of IL-10 promoter polymorphisms (SNPs) with human cancer risks, including risk of lung cancer [6]C[9]. Of the IL-10 promoter SNPs, ones at ?1082A>G, ?819C>T, and ?592G>A have been the focus of recent studies, and the phenotypes of these single nucleotide SNPs have been further confirmed by functional assays in cell models [10], [11]. Tumor immune surveillance studies have revealed an association between IL-10 and the development of human cancers such as large B-cell lymphoma, T-cell non-Hodgkin lymphoma, and colon, prostate, breast, gastric, myeloma, and lung cancers [4], [6]C[9], [12]C[22]. PHA-739358 In lung cancer cases, some reports have indicated that loss of IL-10 in lung tumors may promote tumor progression and result in poor clinical outcomes in patients; however, an opposite effect has been reported in other studies [23]C[29]. Interestingly, the absence of IL-10 expression has been associated with poor outcome in stage I non-small cell lung cancer (NSCLC) [24], [25], while in late-stage NSCLC, the presence of IL-10-positive macrophages at the tumor margins can be an indicator of poor prognostic outcome [23]. In addition, shorter survival occasions have been reported in advanced lung PHA-739358 cancer patients who had high serum IL-10 levels, when compared with similar patients who had low serum IL-10 levels [26]. A clear role for IL-10 in lung tumorigenesis therefore remains to be identified. In the present study, we examined normal lung tissues adjacent to surgically resected NSCLC tumors in 385 patients in order to identify IL-10 promoter SNPs at ?1082A>G, ?819C>T, and ?592C>A by direct sequencing and polymerase chain reaction restriction fragment Rabbit Polyclonal to TOR1AIP1 length polymorphism (PCR-RFLP). These three IL-10 promoter SNPs have been reported to produce mainly three haplotypes: GCC, ACC, ATA [30]C[33]. In the present study, patients were categorized into two haplotypes, ATA and non-ATA (Fig. 1), PHA-739358 which had been used in two previous reports [34], [35]. We questioned: 1) whether tumors from non-ATA carriers PHA-739358 have higher IL-10 mRNA expression levels than tumors from ATA carriers, 2) whether patients with a non-ATA haplotype or higher IL-10 mRNA levels in lung tumors have greater tumor immune PHA-739358 surveillance, and 3) whether IL-10 haplotype or mRNA expression could be used to predict overall survival (OS) and relapse free survival (RFS) in resected NSCLC patients. Physique 1 Allele/haplotype frequencies of IL-10 SNPs. Materials and Methods Patients This study included 385 patients with NSCLC. All patients were unrelated ethnic Chinese and residents of central Taiwan. Patients had been diagnosed with adenocarcinoma (194; 50.4%) or squamous cell carcinoma (191; 49.6%) and underwent surgical resection at the Division of Thoracic Surgery, Taichung Veterans General.