Immunosuppressive effect of regulatory T lymphocytes in lung cancer, with special reference to their effects on the induction of autologous tumor-specific cytotoxic T lymphocytes

Shigematsu, Yoshiki; Hanagiri, Takeshi; Shiota, Hironobu; Kuroda, Koji; Baba, Tetsuro; Ichiki, Yoshinobu; Yasuda, Manabu; Uramoto, Hidetaka; Takenoyama, Mitsuhiro; Yasumoto, Kosei; Tanaka, Fumihiro

doi:10.3892/ol.2012.815

Cited by 25 publications

(17 citation statements)

References 41 publications

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“…Some studies have shown that during the early stage of differentiation, Treg cells may require TGF-β, which is secreted by TAMs, to hamper immunoregulatory responses (15). Other studies have demonstrated that Treg cells may mediate immunosuppression by IL-10 in the tumor microenvironment (25)(26)(27). With respect to Treg cells, Islas-Vazquez et al proposed that IL-10 may participate in the differentiation process of Treg cells in lung adenocarcinoma (28).…”

Section: Discussionmentioning

confidence: 99%

Interaction between Treg cells and tumor-associated macrophages in the tumor microenvironment of epithelial ovarian cancer

Zhu

et al. 2016

Oncology Reports

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Abstract. Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy. Inflammatory cells in the EOC microenvironment play a key role in tumor progression. In the present study, we investigated the mechanism of the accumulation of regulatory T cells (Tregs) induced by interleukin-10 (IL-10) derived from tumor-associated macrophages (TAMs) in the EOC microenvironment. The frequency of Tregs and TAMs was detected by immunofluorescence in 40 EOC tissues and 20 benign ovarian tumors, as well as the expression of IL-10 which was assessed by immunohistochemistry. It was found that the frequency of Treg cells and TAMs was significantly higher in the EOC than those in the benign ovarian tumors. The expression of IL-10 was also found to be higher in the EOC than that in the benign tumors. EOC patients with a high frequency of Tregs exhibited a significantly shorter overall survival time compared to those with a low frequency of Tregs. In addition, the expression of IL-10 in ascites and blood serum and the IL-10 released in the co-cultured system supernatants were detected by ELISA. Following CD4 + T-cell co-culturing with macrophages and IL-10, it was observed by flow cytometric analysis that the frequency of Treg cells was increased in the presence of IL-10. It was also established that IL-10 released in the co-cultured supernatants was increased. We also detected the mechanism of Treg cells induced by IL-10 in vivo. The SKOV3 cell tumor volume and weight were much higher in the presence of IL-10 in a mouse subcutaneous model. These data suggest that IL-10 secreted by TAMs increase the frequency of Treg cells through the activation of Foxp3 during T-cell differentiation and promotes tumor progression.

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Section: Discussionmentioning

confidence: 99%

Interaction between Treg cells and tumor-associated macrophages in the tumor microenvironment of epithelial ovarian cancer

Zhu

et al. 2016

Oncology Reports

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“…+ Treg cells, as a minor yet important group of T cells, mediate immune suppression and immune incompetency, and play a role in negative immune regulation and maintain the stability of the internal environment of an organism through contacts between cells and cytokine secretion (Shigematsu et al, 2012). CD127, as the alphachain receptor of IL-7, has been shown to play an important role in the proliferation, differentiation, and maturation of T cells.…”

Section: Discussionmentioning

confidence: 99%

Changes of circulating CD4+CD25+CD127low regulatory T cells in patients with acute coronary syndrome and its significance

M¹,

Liu²,

Jx³

2015

Genet. Mol. Res.

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ABSTRACT. The aim of this study was to investigate the changes of circulating CD4 + CD25 + CD127 low regulatory T cells (Treg) in patients with acute coronary syndrome (ACS) and its significance. The experiment was divided into three groups: ACS (48 patients), stable angina pectoris (SAP) (24 patients), and normal controls (24 subjects). The CD4low Treg cell counts were tested by flow cytometry, and the levels of high-sensitivity C-reactive protein (hs-CRP) and peripheral blood leukocytes (PWBCs) were determined in the peripheral blood of each group; comparisons were made among groups. The frequency of CD4 + CD25 + CD127low to CD4 + cell in the ACS group (3.18 ± 1.76%) was significantly lower than those observed in control (5.64 ± 1.63%) and SAP (5.60 ± 1.56%) groups (F = 25.247, P < 0.01), while the hs-CRP and PWBC levels in the ACS group were significantly higher than those in the control group (P < 0.05). In addition, the reduced frequency of CD4 + CD25 + CD127 low to CD4 + cells was negatively correlated with the increased hs-CRP and PWBC counts by correlation analysis, and the related coefficients (r) were -0.518 and (2015) -0.311, respectively (P < 0.01). These findings indicate that the decrease of the frequency of Treg cells in the peripheral blood of patients with ACS might destroy the balance of tolerance of the peripheral immune system and might activate inflammation, thus participating in the occurrence and development of the pathological processes of atherosclerosis.

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“…Tregs are thought to be a major cause of tumor-driven immune evasion, which is a major obstacle to the development of effective immunotherapies. Our previous studies demonstrated that the Tregs in the regional lymph nodes of NSCLC patients inhibited the induction of cytotoxic T lymphocytes (CTLs) against autologous tumor cells, and the depletion of Tregs restored the induction of CTLs [18]. Foxp3 has been used as hallmark of Tregs, because it is a master regulator for the differentiation and function of Tregs [19].…”

Section: Discussionmentioning

confidence: 99%

Indoleamine 2,3-Dioxygenase as A Prognostic Factor in Patients with Non-Small Cell Lung Cancer

Fukumoto¹

2014

J Clin Cell Immunol

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Background: Indoleamine 2,3-dioxygenase (IDO) is an immunomodulatory enzyme produced by tumor cells and some alternatively activated macrophages and other immunoregulatory cells. The purpose of the present study was to evaluate the prognostic value of the relative expression of the forkhead/winged helix transcription factor 3 (Foxp3) and IDO in non-small cell lung cancer (NSCLC) tissues. Methods:The NSCLC tissues from 141 patients who underwent complete surgical resection were collected at the time of surgery. The relative expression levels of Foxp3 and IDO in the tissues were determined by quantitative RT-PCR. Results:The histological types of cancer seen in these patients included 105 adenocarcinomas, 24 squamous cell carcinomas and 12 other types of carcinoma. The average expression levels of Foxp3 and IDO relative to that of β-actin in the NSCLC tissue were 0.052 ± 0.147% and 0.088 ± 0.157%, respectively. The relative expression of Foxp3 tended to increase with the relative expression of IDO (R=0.451, P=0.001). The five-year survival rates of the patients according to the relative expression of Foxp3 were 78.3% and 71.9% in the lower and higher groups, respectively. According to the relative expression of IDO, the five-year survival rate was 83.2% in the lower expression group, and 67.9% in the higher expression group. There was a significant difference between the lower and higher IDO expression groups (p=0.0389). Conclusions:The expression of IDO tended to have a positive correlation with the expression of Foxp3. The higher expression of IDO was therefore a significantly unfavorable prognostic factor in patients with NSCLC.

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Immunosuppressive effect of regulatory T lymphocytes in lung cancer, with special reference to their effects on the induction of autologous tumor-specific cytotoxic T lymphocytes

Cited by 25 publications

References 41 publications

Interaction between Treg cells and tumor-associated macrophages in the tumor microenvironment of epithelial ovarian cancer

Interaction between Treg cells and tumor-associated macrophages in the tumor microenvironment of epithelial ovarian cancer

Changes of circulating CD4+CD25+CD127low regulatory T cells in patients with acute coronary syndrome and its significance

Indoleamine 2,3-Dioxygenase as A Prognostic Factor in Patients with Non-Small Cell Lung Cancer

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