Background
Polyinosinic-polycytidylic acid sodium(Poly I:C) is a synthetic dsRNA that can imitate a viral infection and elicit host immune responses by triggering specific pattern-recognition receptors (PRRs) such as toll-like receptor 3(TLR3) and retinoic acid inducible gene I(RIG-I)-like receptors, including RIG-I and melanoma differentiation-associated gene 5. Poly I:C can be used as a vaccine adjuvant for cancer immunotherapy[1-3].
poly(I:C)(20 μg in 0.2 mL of cell suspension)-electroporated AML cells potently activate DC and NK cell functions and stimulate NK-DC cross-talk in terms of tumor cell killing[4]. Activation of the TLR3 signaling pathway in cancer cells through poly I:C(100 μg/ml;72 h) makes Hela cells (human cervical cancer) dose-dependent sensitive to apoptosis induced by the protein synthesis inhibitor cycloheximide (CHX) [5].
Poly I:C(10 μg/g;p.o.) exposure induces severe intestinal injury and inflammation[6]. Pre-treatment with the viral TLR3 agonist poly(I:C) (20/200 μg) modulated innate immune responses and strengthened the resistance of neutropenic mice against E. coli K1 meningoencephalitis[7].The intratumoral synergistic combination of poly(I:C)(25 μg;i.p; six times from day9-day21)+R848 significantly prevented tumor growth and metastasis in lung cancer and fibrosarcoma immunocompetent murine models[8].
Polyinosinic-polycytidylic acid sodium (Poly I:C)是一种合成的dsRNA,可以模拟病毒感染,并通过触发特定的模式识别受体(PRRs),如toll样受体3(TLR3)和维甲酸诱导基因I(RIG-I)样受体,包括RIG-I和黑色素瘤分化相关基因5,引发宿主免疫反应。Poly I:C可作为癌症免疫治疗的疫苗佐剂[1-3]。
Poly I:C (20μg)电穿孔AML细胞能有效激活DC和NK细胞功能,并在杀伤肿瘤细胞方面刺激NK-DC串扰[4]。poly I:C(100 μg/ml;72 h)激活癌细胞中TLR3信号通路,使Hela细胞(人宫颈癌)对蛋白质合成抑制剂环己亚胺(cycloheximide, CHX)诱导的凋亡呈剂量依赖性敏感[5]。
Poly I:C(10μg/g;p.o.)可引起严重的肠道损伤和炎症[6]。用病毒性TLR3激动剂poly(I:C)(20/200μg)预处理可调节先天免疫反应,增强中性粒细胞减少小鼠对大肠杆菌K1脑膜脑炎的抵抗力[7]。肿瘤内poly(I:C) (25 μg;i.p; six times from day9-day21)+R848的协同组合可显著阻止肺癌和纤维肉瘤免疫活性小鼠模型的肿瘤生长和转移[8]。
参考文献:
[1]. Zhao X, Ai M, et,al. Poly I:C-induced tumor cell apoptosis mediated by pattern-recognition receptors. Cancer Biother Radiopharm. 2012 Nov;27(9):530-4. doi: 10.1089/cbr.2012.1226. Epub 2012 Oct 12. PMID: 23062195.
[2]. Zhao X, Ai M, et,al.Poly I:C-induced tumor cell apoptosis mediated by pattern-recognition receptors. Cancer Biother Radiopharm. 2012 Nov;27(9):530-4. doi: 10.1089/cbr.2012.1226. Epub 2012 Oct 12. PMID: 23062195.
[3]. Kato H, Takeuchi O, et,al.Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. Nature. 2006 May 4;441(7089):101-5. doi: 10.1038/nature04734. Epub 2006 Apr 9. PMID: 16625202.
[4]. Lion E, Anguille S, et,al.Poly(I:C) enhances the susceptibility of leukemic cells to NK cell cytotoxicity and phagocytosis by DC. PLoS One. 2011;6(6):e20952. doi: 10.1371/journal.pone.0020952. Epub 2011 Jun 17. PMID: 21698118; PMCID: PMC3117863.
[5]. Jiang Q, Wei H, et,al.Poly I:C enhances cycloheximide-induced apoptosis of tumor cells through TLR3 pathway. BMC Cancer. 2008 Jan 17;8:12. doi: 10.1186/1471-2407-8-12. PMID: 18199340; PMCID: PMC2242792.
[6]. Ginzel M, Yu Y, et,al.The viral dsRNA analogue poly (I:C) induces necrotizing enterocolitis in neonatal mice. Pediatr Res. 2016 Apr;79(4):596-602. doi: 10.1038/pr.2015.261. Epub 2015 Dec 17. PMID: 26679153.
[7]. Ribes S, Arcilla C, et,al.Pre-treatment with the viral Toll-like receptor 3 agonist poly(I:C) modulates innate immunity and protects neutropenic mice infected intracerebrally with Escherichia coli. J Neuroinflammation. 2020 Jan 17;17(1):24. doi: 10.1186/s12974-020-1700-4. PMID: 31952519; PMCID: PMC6969464.
[8]. Anfray C, Mainini F, et,al.Intratumoral combination therapy with poly(I:C) and resiquimod synergistically triggers tumor-associated macrophages for effective systemic antitumoral immunity. J Immunother Cancer. 2021 Sep;9(9):e002408. doi: 10.1136/jitc-2021-002408. PMID: 34531246; PMCID: PMC8449972.
Protocol
| Cell experiment [1]: |
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Cell lines
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Hela cells
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Preparation Method
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Tumor cells were cultured with poly I:C (100 μg/ml) alone, CHX (1.5 μg/ml) alone or poly I:C plus CHX for 72 h.
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Reaction Conditions
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100 μg/ml;72 h
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Applications
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Poly I:C treatment caused tumor cells more sensitive to CHX-induced cell death.
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| Animal experiment [2]: |
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Animal models
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Four-d-old C57BL/6J pups
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Preparation Method
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Mice were stressed by asphyxia and hypothermia twice daily. Mice were either fed by formula only (FO), formula containing LPS or poly I:C . After 72 h, mice were euthanized.
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Dosage form
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10 μg/g;p.o.
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Applications
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Poly I:C exposure induces severe intestinal injury and inflammation.
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参考文献:
[1]. Jiang Q, Wei H, et,al.Poly I:C enhances cycloheximide-induced apoptosis of tumor cells through TLR3 pathway. BMC Cancer. 2008 Jan 17;8:12. doi: 10.1186/1471-2407-8-12. PMID: 18199340; PMCID: PMC2242792.
[2].Ginzel M, Yu Y, et,al.The viral dsRNA analogue poly (I:C) induces necrotizing enterocolitis in neonatal mice. Pediatr Res. 2016 Apr;79(4):596-602. doi: 10.1038/pr.2015.261. Epub 2015 Dec 17. PMID: 26679153.
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