Abstract
IL-10 is associated with tumor malignancy via immune escape. We hypothesized that IL-10 haplotypes categorized by IL-10 promoter polymorphisms at –1082A>G, –819C>T, and –592C>A might influence IL-10 expression and give rise to non-small cell lung cancer (NSCLC) patients with poor outcomes and relapse. We collected adjacent normal tissues from 385 NSCLC patients to determine IL-10 haplotypes by direct sequencing and polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Of the 385 tumors, 241 were available to evaluate IL-10 mRNA expression levels by real-time RT-PCR. The influence of IL-10 haplotypes on overall survival (OS) and relapse free survival (RFS) were determined by Kaplan-Meier and multivariate Cox regression analysis. The results showed that IL-10 mRNA levels were significantly higher in tumors with the non-ATA haplotype than with the ATA haplotype (P = 0.004). Patients with the non-ATA haplotype had shorter OS and RFS periods than did patients with the 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.
Highlights
Interleukin-10 (IL-10), an important immunoinhibitory cytokine, is part of a balanced network of cytokines [1,2,3,4,5]
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 non-small cell lung cancer (NSCLC), helping clinicians to make appropriate decisions on treatment of the patients
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]
Summary
Interleukin-10 (IL-10), an important immunoinhibitory cytokine, is part of a balanced network of cytokines [1,2,3,4,5]. Many case-control studies have indicated an association of IL-10 promoter polymorphisms (SNPs) with human cancer risks, including risk of lung cancer [6,7,8,9]. 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 [4,6,7,8,9,12,13,14,15,16,17,18,19,20,21,22]. 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]. A clear role for IL-10 in lung tumorigenesis remains to be identified
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