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出芽短梗霉 β-葡聚糖通过激活肿瘤相关树突状细胞增强抗肿瘤免疫反应。

β-glucan from Aureobasidium pullulans augments the anti-tumor immune responses through activated tumor-associated dendritic cells.

机构信息

Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Division of Transplantation Immunology, National Research Institute for Child Health and Development, Tokyo, Japan; Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Division of Transplantation Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.

出版信息

Int Immunopharmacol. 2021 Dec;101(Pt A):108265. doi: 10.1016/j.intimp.2021.108265. Epub 2021 Oct 29.

DOI:10.1016/j.intimp.2021.108265
PMID:34715491
Abstract

Dendritic cells (DCs) are recognized as the most potent antigen-presenting cells, capable of priming both naïve and memory T cells. Thus, tumor-resident DCs (tumor-associated DCs: TADCs) play a crucial role in the immune response against tumors. However, TADCs are also well known as a "double-edged sword" because an immunosuppressive environment, such as a tumor microenvironment, maintains the immature and tolerogenic properties of TADCs, resulting in the deterioration of the tumor. Therefore, it is essential to maintain and enhance the anti-tumoral activity of TADCs to aid tumor elimination. This study demonstrated the potential for tumor growth inhibition of Aureobasidium pullulan-derived β-glucan (AP-BG). Administration of AP-BG dramatically limited the development of different types of tumor cell lines transplanted into mice. Examination of the tumor-infiltrating leukocytes revealed that AP-BG caused high expression of co-stimulatory molecules on TADCs and enhanced the production of cytolytic granules as well as pro-inflammatory cytokines by the tumor-resident T cells. Furthermore, the syngeneic mixed lymphoid reaction assay and popliteal lymph node assay showed the significant ability of AP-BG to improve DCs' antigen-specific priming of T cells in vitro and in vivo. Taken together, β-glucan might be an immune-potentiating adjuvant for cancer treatment. This highly widely-used reagent will initiate a new way to activate DC-targeted cancer immune therapy.

摘要

树突状细胞 (DCs) 被认为是最有效的抗原呈递细胞,能够激活初始和记忆 T 细胞。因此,肿瘤驻留树突状细胞 (肿瘤相关树突状细胞:TADCs) 在抗肿瘤免疫反应中起着至关重要的作用。然而,TADCs 也被称为“双刃剑”,因为肿瘤微环境等免疫抑制环境会保持 TADCs 的不成熟和耐受性特性,从而导致肿瘤恶化。因此,维持和增强 TADCs 的抗肿瘤活性对于帮助肿瘤消除至关重要。本研究证明了出芽短梗霉来源的β-葡聚糖 (AP-BG) 具有抑制肿瘤生长的潜力。AP-BG 的给药显著限制了移植到小鼠体内的不同类型肿瘤细胞系的发展。对肿瘤浸润白细胞的检查表明,AP-BG 导致 TADCs 上共刺激分子的高表达,并增强了肿瘤驻留 T 细胞产生细胞毒性颗粒和促炎细胞因子的能力。此外,同种混合淋巴细胞反应测定和腘淋巴结测定显示,AP-BG 具有显著提高 DC 体外和体内对 T 细胞抗原特异性启动的能力。综上所述,β-葡聚糖可能是癌症治疗的免疫增强佐剂。这种广泛使用的试剂将为激活针对 DC 的癌症免疫治疗开辟新途径。

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