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利用从 中提取的多糖进行癌症免疫疗法的研究。

Cancer immunotherapy using a polysaccharide from in a murine model.

机构信息

Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.

Department of Medical Biotechnology, Yeungnam University, Gyeongsan, South Korea.

出版信息

Oncoimmunology. 2020 Jun 1;9(1):1772663. doi: 10.1080/2162402X.2020.1772663.

Abstract

UNLABELLED

Natural polysaccharides have shown immune modulatory effects with low toxicity in both animal and human models. A previous study has shown that the polysaccharide from (CFP) promotes natural killer (NK) cell activation in mice. Since NK cell activation is mediated by dendritic cells (DCs), we examined the effect of CFP on DC activation and evaluated the subsequent induction of anti-cancer immunity in a murine model. Treatment with CFP induced activation of bone marrow-derived dendritic cells (BMDCs). Moreover, subcutaneous injection of CFP promoted the activation of spleen and lymph node DCs . CFP also induced activation of DCs in tumor-bearing mice, and combination treatment with CFP and ovalbumin (OVA) promoted OVA-specific T cell activation, which consequently promoted infiltration of IFN-γ-and TNF-α-producing OT-1 and OT-II cells into the tumors. Moreover, combination treatment using CFP and cancer self-antigen efficiently inhibited B16 tumor growth in the mouse model. Treatment with CFP also enhanced anti-PD-L1 antibody mediated anti-cancer immunity in the CT-26 carcinoma-bearing BALB/c mice. Taken together these data suggest that CFP may function as an adjuvant in the treatment of cancer by enhancing immune activation.

ABBREVIATIONS

CFP: polysaccharide; NK: natural killer; IFN: interferon; TNF: tumor necrosis factor; IL: interleukin; tdLN: tumor draining lymph node; BMDC: bone marrow-derived dendritic cell; OVA: ovalbumin; Ab: antibody; Ag: antigen; DC: dendritic cell; CTL: cytotoxic T lymphocyte; APC: antigen-presenting cell; pDC: plasmacytoid dendritic cell; mDC: myeloid dendritic cell; MHC: major histocompatibility complex; CR3: complement receptor type 3; TLR: Toll-like receptor; LPS: lipopolysaccharide; SP: sulfated polysaccharide; TRP2: tyrosinase-related protein 2; SR-A: scavenger receptor-A.

摘要

未加标签

天然多糖在动物和人体模型中均显示出具有低毒性的免疫调节作用。先前的研究表明, (CFP)中的多糖可促进小鼠自然杀伤(NK)细胞的激活。由于 NK 细胞的激活是由树突状细胞(DC)介导的,我们研究了 CFP 对 DC 激活的影响,并在小鼠模型中评估了随后对抗癌免疫的诱导。CFP 处理诱导骨髓来源的树突状细胞(BMDC)的激活。此外,CFP 的皮下注射促进了脾脏和淋巴结 DC 的激活 。CFP 还诱导荷瘤小鼠中 DC 的激活,并且 CFP 与卵清蛋白(OVA)的联合治疗促进了 OVA 特异性 T 细胞的激活,进而促进 IFN-γ和 TNF-α产生的 OT-1 和 OT-II 细胞浸润到肿瘤中。此外,CFP 和癌症自身抗原的联合治疗有效地抑制了小鼠模型中的 B16 肿瘤生长。CFP 处理还增强了 CT-26 荷瘤 BALB/c 小鼠中抗 PD-L1 抗体介导的抗癌免疫。总之,这些数据表明 CFP 可通过增强免疫激活而作为癌症治疗的佐剂。

缩写

CFP:多糖;NK:自然杀伤;IFN:干扰素;TNF:肿瘤坏死因子;IL:白细胞介素;tdLN:肿瘤引流淋巴结;BMDC:骨髓来源的树突状细胞;OVA:卵清蛋白;Ab:抗体;Ag:抗原;DC:树突状细胞;CTL:细胞毒性 T 淋巴细胞;APC:抗原呈递细胞;pDC:浆细胞样树突状细胞;mDC:髓样树突状细胞;MHC:主要组织相容性复合体;CR3:补体受体 3;TLR:Toll 样受体;LPS:脂多糖;SP:硫酸多糖;TRP2:酪氨酸酶相关蛋白 2;SR-A:清道夫受体-A。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0dda/7458636/13d46296d216/KONI_A_1772663_F0001_B.jpg

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