Integrated Expression Profiles Analysis Reveals Correlations Between the IL-33/ST2 Axis and CD8(+) T Cells, Regulatory T Cells, and Myeloid-Derived Suppressor Cells in Soft Tissue Sarcoma.
Integrated Expression Profiles Analysis Reveals Correlations Between the IL-33/ST2 Axis and CD8(+) T Cells, Regulatory T Cells, and Myeloid-Derived Suppressor Cells in Soft Tissue Sarcoma.
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整合表达谱分析揭示软组织肉瘤中 IL-33/ST2 轴与 CD8( ) T 细胞、调节性 T 细胞和骨髓源性抑制细胞之间的相关性
DOI：
10.3389/fimmu.2018.01179
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发表时间：
2018
影响因子：
7.3
通讯作者：
Zheng F
中科院分区：
文献类型：
--
作者：
Chen H;Chen Y;Liu H;Que Y;Zhang X;Zheng F
软组织肉瘤（STS）是一种罕见的实体恶性肿瘤，并且对于晚期疾病几乎没有有效的治疗选择。肿瘤免疫治疗是STS治疗的一个有前途的新策略。IL-33是免疫治疗的候选细胞因子，其可以激活T淋巴细胞并调节某些癌症中的抗肿瘤免疫。然而，IL-33在STS中的表达和生物学作用知之甚少。在这项研究中，我们发现IL-33及其受体ST 2的表达减少STS使用实时PCR检测。通过分析来自癌症基因组图谱的肉瘤数据，我们发现IL-33和ST 2的较高转录水平与有利的结果相关。ST 2与CD 3E、CD 4、CD 8A、CD 45 RO、FOXP 3、CD 11B、CD 33、IFN-γ的表达呈正相关。IFN-γ表达与CD 3E、CD 8A表达呈显著正相关。此外，IL-33和ST 2的表达水平与CD 3E、CD 8A和募集CD 8 + T细胞的趋化因子的表达水平呈正相关，表明IL-33/ST 2轴可能在STS中募集和促进1型极化CD 8 + T细胞的免疫应答中起重要作用。同时，我们还发现IL-33与TGF-β1、趋化因子（募集调节性T细胞（Treg）和髓源性抑制细胞（MDSCs））的表达呈负相关，提示IL-33/ST 2轴可能也参与了STS中拮抗Treg、MDSCs和TGF-β1介导的免疫抑制的作用。通过使用其他三个独立的GEO肉瘤数据集进行额外分析，验证了IL-33/ST 2轴与CD 8 + T细胞和IFN-γ以及TcB、MDSC和TGF-β1之间的相关性。我们的研究结果暗示了IL-33/ST 2轴在STS中调节抗肿瘤免疫的可能作用。IL-33不仅可以作为STS的一个有用的预后生物标志物，而且可以作为STS免疫治疗的一个潜在的治疗靶点，值得进一步研究。
Soft tissue sarcoma (STS) is a rare solid malignant cancer, and there are few effective treatment options for advanced disease. Cancer immunotherapy is a promising new strategy for STS treatment. IL-33 is a candidate cytokine for immunotherapy that can activate T lymphocytes and modulate antitumor immunity in some cancers. However, the expression and biological role of IL-33 in STS are poorly understood. In this study, we found that the expression of IL-33 and its receptor ST2 was decreased in STS using real-time PCR assays. By analyzing sarcoma data from The Cancer Genome Atlas, we found that higher transcriptional levels of IL-33 and ST2 were associated with a favorable outcome. There were positive correlations between the expression levels of ST2 and CD3E, CD4, CD8A, CD45RO, FOXP3, CD11B, CD33, and IFN-γ. Strong positive correlations between the expression of IFN-γ and CD3E and CD8A were also observed. Moreover, the expression levels of both IL-33 and ST2 were positively correlated with those of CD3E, CD8A, and chemokines that recruit CD8+ T cells, indicating that the IL-33/ST2 axis may play an important role in recruiting and promoting the immune response of type 1-polarized CD8+ T cells in STS. Meanwhile, we also found that the expression of IL-33 was negatively correlated with that of TGF-β1 and chemokines that recruit regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs), indicating that the IL-33/ST2 axis may also contribute to antagonizing Tregs, MDSCs, and TGF-β1-mediated immunosuppression in STS. The correlations between the IL-33/ST2 axis and CD8+ T cells and IFN-γ, as well as Tregs, MDSCs, and TGF-β1 were validated by additional analyses using three other independent GEO datasets of sarcoma. Our results implicate the possible role of the IL-33/ST2 axis in modulating antitumor immunity in STS. IL-33 may not only serve as a useful prognostic biomarker for STS but also as a potential therapeutic target for STS immunotherapy and worth further investigation.
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影响因子：
--
作者：
Maki RG;Jungbluth AA;Gnjatic S;Schwartz GK;D'Adamo DR;Keohan ML;Wagner MJ;Scheu K;Chiu R;Ritter E;Kachel J;Lowy I;Old LJ;Ritter G
通讯作者：
Ritter G
影响因子：
7.2
作者：
Lucarini, Valeria;Ziccheddu, Giovanna;Schiavoni, Giovanna
通讯作者：
Schiavoni, Giovanna
DOI：
10.4049/jimmunol.1400481
发表时间：
2014-10-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Matta BM;Lott JM;Mathews LR;Liu Q;Rosborough BR;Blazar BR;Turnquist HR
通讯作者：
Turnquist HR
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
9.7
作者：
Gao, Kun;Li, Xiaoying;Zhang, Lianfeng
通讯作者：
Zhang, Lianfeng