BackgroundExpansions of myeloid-derived suppressor cells (MDSCs) have been identified in human solid tumors, including colorectal cancer (CRC). However, the nature of these tumor-associated MDSCs and their interactions with tumor cells in CRC are still poorly understood.MethodsThe percentages and phenotype of MDSCs in peripheral blood and tumorous and paraneoplastic tissues from CRC patients, as well as the clinical relevance of these MDSCs, were assessed. Age-matched healthy donors were included as controls. The interaction between MDSCs and T cells or tumor cells was investigated in a coculture system in vitro, and the molecular mechanism of the effect of MDSCs on T cells or tumor cells was evaluated.ResultsWe discovered that CRC patients had elevated levels of CD33+CD11b+HLA-DR− MDSCs in primary tumor tissues and in peripheral blood, and the elevated circulating MDSCs were correlated with advanced TNM stages and lymph node metastases. Radical resection significantly decreases the proportions of circulating MDSCs and CD4+CD25highFOXP3+ regulatory T cells. In vitro, CRC cells mediate the promotion of MDSC induction. Moreover, these tumor-induced MDSCs could suppress T cell proliferation and promote CRC cell growth via cell-to-cell contact. Such effects could be abolished by the inhibition of oxidative metabolism, including the production of nitric oxide (NO), and reactive oxygen species (ROS).ConclusionsOur results reveal the functional interdependence between MDSCs, T cells and cancer cells in CRC pathogenesis. Understanding the impact of MDSCs on T cells and tumor cells will be helpful to establish an immunotherapeutic strategy in CRC patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0410-7) contains supplementary material, which is available to authorized users.

The expansion of myeloid-derived suppressor cells (MDSCs) and its correlation with advanced disease stage have been shown in solid cancers. Here, we investigated the functional features and clinical significance of MDSCs in extranodal NK/T cell lymphoma (ENKL). A higher percentage of circulating HLA-DR−CD33+CD11b+ MDSCs was observed in ENKL patients than in healthy controls (P < 0.05, n = 32) by flow cytometry analysis. These MDSCs from ENKL patients (ENKL-MDSCs) consisted of CD14+ monocytic (Mo-MDSCs, >60 %) and CD15+ granulocytic (PMN-MDSCs, <20 %) MDSCs. Furthermore, these ENKL-MDSCs expressed higher levels of Arg-1, iNOS and IL-17 compared to the levels of MDSCs from healthy donors, and they expressed moderate levels of TGFβ and IL-10 but lower levels of CD66b. The ENKL-MDSCs strongly suppressed the anti-CD3-induced allogeneic and autologous CD4 T cell proliferation (P < 0.05), but they only slightly suppressed CD8 T cell proliferation (P > 0.05). Interestingly, ENKL-MDSCs inhibited the secretion of IFNγ but promoted IL-10, IL-17 and TGFβ secretion as well as Foxp3 expression in T cells. The administration of inhibitors of iNOS, Arg-1 and ROS significantly reversed the suppression of anti-CD3-induced T cell proliferation by MDSCs (P < 0.05). Importantly, based on multivariate Cox regression analysis, the HLA-DR−CD33+CD11b+ cells and CD14+ Mo-MDSCs were independent predictors for disease-free survival (DFS, P = 0.013 and 0.016) and overall survival (OS, P = 0.017 and 0.027). Overall, our results identified for the first time that ENKL-MDSCs (mainly Mo-MDSCs) have a prognostic value for patients and a suppressive function on T cell proliferation.Electronic supplementary materialThe online version of this article (doi:10.1007/s00262-015-1765-6) contains supplementary material, which is available to authorized users.

AimTo identify risk factors for lymph node metastasis using a nomogram for gastric cancer patients to predict lymph node metastasis.ResultsThe Chi-square test and the logistic regression showed that the Boarrmann type, preoperative CA199 level, T stage and N stage by CT scan were independent risk factors. The concordance index (C-index) was 0.786 in the internal validation of the Nomogram model. In the external validation, the C-index was 0.809, and the AUC was 0.894. The total accuracy of the prediction was 82.2%, and the false-negative rate was 5.4% with a cut-off value set at 0.109.Materials and MethodsThe study consisted of 451 patients with a histological diagnosis of gastric cancer with 0 or 1 lymph node metastasis from the Sun Yat-sen University Cancer Center as the development set, and the validation set consisted of 186 gastric cancer patients from the Sixth Affiliated Hospital of Sun Yat-Sen University. A Chi-square test and a logistic regression analysis were used to compare the clinicopathological variables and lymph node metastasis. The C-index and ROC curve were computed for comparisons of the nomogram's predictive ability.ConclusionsWe developed and validated a nomogram to predict lymph node metastasis in gastric cancer before surgery. This nomogram can be broadly applied, even in general hospitals, and is useful for decisions regarding treatment programs for patients.

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Aim. To investigate whether tumor size is a reasonable indication for adjuvant chemotherapy for T3-4aN0M0 gastric cancer patients after D2 gastrectomy. Method. We performed a retrospective study of 269 patients with a histological diagnosis of T3-4aN0M0 stage gastric cancer who underwent D2 radical surgery at the Sun Yat-sen University Cancer Center or the Sixth Affiliated Hospital of Sun Yat-sen University between January 2006 and December 2010. The follow-up lasted until June of 2015. Chi-square tests and Kaplan-Meier methods were employed to compare the clinicopathological variables and prognoses. Result. For this group of patients, univariate analyses revealed that tumor size (p < 0.001), pathological T stage (p < 0.001), and tumor location (p = 0.025) were significant prognostic factors. Adjuvant chemotherapy did not exhibit prognostic benefits. For patients with tumors larger than 5 cm, univariate analysis revealed that tumor location (p = 0.007), Borrmann type (p = 0.039), postoperative chemotherapy (p = 0.003), and pathological T stage (p < 0.001) were significant prognostic factors. Multivariate analysis revealed that postoperative chemotherapy and pathological T stage were independent prognostic factors. Conclusion. Our results imply that tumor size should be a critical factor in the decision to utilize adjuvant chemotherapy for T3-4aN0M0 gastric cancer patients after D2 gastrectomy. Additional randomized controlled trials are required before this conclusion can be considered definitive.