Increased numbers of gastric-infiltrating mast cells and regulatory T cells are associated with tumor stage in gastric adenocarcinoma patients

Department of Gastrointestinal Surgery and Minimal Invasive Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, P.R. China.
Oncology letters (Impact Factor: 1.55). 10/2012; 4(4):755-758. DOI: 10.3892/ol.2012.830
Source: PubMed


Mast cells (MCs) and regulatory T cells (Tregs) are the important components of the inflammatory infiltrating leukocytes in most malignant tumors. Our study was designed to investigate the infiltrating correlation between MCs and Tregs and clarify their prognostic significance in gastric cancer (GC). A total of 60 fresh GC tissues were collected and tumor-infiltrating leukocytes were isolated by gradient centrifugation. Tryptase and Foxp3 were used as markers for MCs and Tregs, respectively. The expression of tryptase and Foxp3 was determined in tumor-infiltrating leukocytes using flow cytometry. The expression of tryptase and Foxp3 were positively correlated. The increased infiltration of MCs correlated significantly with advanced stage of GC. The infiltration of MCs into the tumor may increase the number of Tregs. Tryptase is a promising marker to stratify GC patients into different risk groups.

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    • "Up to now, the role of MCs in gastric cancer angiogenesis has not been clarified completely. We have a lot of data about the angiogenic process and its drug targets in tumours [19, 20], but there are few data on the role of MCs in gastric cancer angiogenesis [14, 21]. In particular, in a study designed by Mukherjee et al. [22], the authors studied MCs density in patients with gastric ulcers, well-differentiated cancers, and poorly differentiated cancers. "
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    ABSTRACT: Background. Angiogenesis is a complex process involved in both growth and progression of several human and animal tumours. Tryptase is a serin protease stored in mast cells granules, which plays a role in tumour angiogenesis. Mast cells (MCs) can release tryptase following c-Kit receptor (c-KitR) activation. Method. In a series of 25 gastric cancer patients with stage T3N2-3M0 (by AJCC for Gastric Cancer 7th Edition), immunohistochemistry and image analysis methods were employed to evaluate in the tumour tissue the correlation between the number of mast cells positive to tryptase (MCPT), c-KitR expressing cells (c-KitR-EC), and microvascular density (MVD). Results. Data demonstrated a positive correlation between MCPT, c-KitR-EC, and MVD to each other. In tumour tissue the mean number of MCPT was 15, the mean number of c-KitR-EC was 20, and the mean number of MVD was 20. The Pearson test correlating MCPT and MVD, c-KitR-EC and MVD was significantly (r = 0.64, P = 0.001; r = 0.66, P = 0.041, resp.). Conclusion. In this pilot study, we suggest that MCPT and c-KitR-EC play a role in gastric cancer angiogenesis, so we think that several c-KitR or tryptase inhibitors such as gabexate mesilate and nafamostat mesilate might be evaluated in clinical trials as a new antiangiogenetic approach.
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    ABSTRACT: Objective: This research explores the relationship between the immuno-suppression function of regulatory T cells (Treg) in the ascites of ovarian cancer (OC) patients, the clinico-pathologic features of these patients, and the correlation of the function of Treg with initial treatment and relapse status of the patients to further investigate the specific mechanism of immuno-regulatory function of CD4+ CD25+ Treg in the ascites of OC. Methods: Immuno-magnetic activated cell sorting (MACS) was conducted to sort CD4+ CD25+ Treg and autologous CD4+ CD25- Treg from the ascites of 28 OC patients. Carboxyfluorescein-diacetate succinimidyl ester (CFSE) was used to label the autologous CD4+ CD25- Treg. These labeled cells were then used as controls and co-cultured with autologous CD4+ CD25+ Treg at the ratio of 1:1 or 1:2. The mean inhibition ratio of Treg in specimens to the proliferation of autologous CD4+ CD25- Treg was calculated after the flow cytometry of the CFSE expression and Modfit software analysis of the CD4+ CD25- Treg proliferation index (PI) were performed. Anti-IL-10 and/or anti-TGF-β1 antibodies were neutralized to investigate whether the CD4+ CD25+ Treg-mediated immuno-suppression escaped through the ascites can produce a marked effect by the inhibitory cytokine IL-10 or TGF-β1. Results: The mean inhibition ratio of CD4+ CD25- Treg in the ascites of stage III to IV OC patients was (75.72±17.04)%, which is significantly higher than that of stage I to II OC patients (59.61±16.97) %; P<0.05. In addition, Treg in the ascites of OC patients with recurrent disease showed a significantly higher inhibition ratio than that of patients with primary disease; P< 0.001. Moreover, Treg in groups added into neutralizing anti-IL-10 and/or anti-TGF-β1 antibodies displayed significantly lower depressant effect than the control group; P<0.05. Conclusion: The immuno-suppression of CD4+ CD25+ Treg in the ascites of OC patients is correlated with the tumor staging and status of the primary or recurrent diseases. Moreover, Treg may indicate a suppressor function by secreting cytokine IL-10 and TGF-β1.
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    ABSTRACT: Objective: CD4+ CD25+ regulatory T cells (Treg) may contribute to tumor progression by suppressing antitumor immunity. The function of Treg in antitumor immunity regulation in the peritoneal microenvironment of ovarian cancer (OC) was investigated and compared with the circulating Treg to elucidate OC immune escape. Methods: Flow cytometry was used to determine the proportion of CD4+ CD25+ T cells in CD4+ T cells in ascites of 27 patients with OC and in peripheral blood lymphocytes of 28 patients with OC. The samples were analyzed and classified in three stages: primary disease (PD), after chemotherapy (AC), and recurrence disease (RD), according to the clinical conditions of the OC patients upon donating the samples. The percentage of Treg in the three groups was determined in ascites and blood. CD4+ CD25+ T cells were isolated from ascites and peripheral blood of patients with OC using magnetic sorting (MACS) system. The cells were then tested for regulatory function through coculture with carboxyfluorescein diacetate succinimidyl ester-labeled autologous CD4 + CD25- responder cells. Results: The proportion of CD4+ CD25+ T cells in CD4+ T cells significantly increased in ascites (28.25% ± 14.06%) compared with that in blood (14.6% ± 4.74%;P<0.0001). The Treg in ascites and blood in AC showed higher proportion (P<0.0001) than those in the PD and RD; the proportion in RD was higher than that in PD (P<0.0001). Moreover, the Treg in ascites mediated a significantly higher suppression compared with the Treg in peripheral blood (P<0.001). Conclusion: The frequency and suppressor function of Treg were significantly higher in ascites than in peripheral blood. This finding suggests more possibility for escape immune surveillance in the peritoneal microenvironment. Moreover, the proportion of Treg in AC was higher than that in PD or RD; the proportion in RD was higher than that in the PD. Chemotherapy may favor the expansion of Treg, which may promote the recurrence of cancer.
    No preview · Article · Jun 2014
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