Cowpea mosaic virus stimulates antitumor immunity through recognition by multiple MYD88-dependent toll-like receptors.
Cowpea mosaic virus stimulates antitumor immunity through recognition by multiple MYD88-dependent toll-like receptors.
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DOI：
10.1016/j.biomaterials.2021.120914
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发表时间：
2021-08
期刊：
影响因子：
14
通讯作者：
Fiering S
中科院分区：
文献类型：
--
作者：
Mao C;Beiss V;Fields J;Steinmetz NF;Fiering S
豇豆花叶病毒（CPMV），一种无包膜的植物病毒，和空CPMV（eCPMV），一种病毒样颗粒（VLP）组成的CPMV衣壳没有核酸，是有效的原位癌症疫苗时，肿瘤内（I.T.）。然而，目前还不清楚免疫细胞如何识别这些纳米颗粒以及为什么它们具有免疫原性，这在本研究中进行了研究。CPMV在幼稚小鼠脾细胞中产生更强的细胞因子和趋化因子的选择性诱导，并且表现出比eCPMV更有效的抗肿瘤功效。MyD 88是CPMV和eCPMV引起的免疫应答所必需的。使用人胚肾（HEK）-293细胞toll样受体（TLR）报告基因测定进行筛选，沿着在相应TLR−/−小鼠中进行的实验表明，CPMV和eCPMV衣壳被MyD 88依赖性TLR 2和TLR 4识别。CPMV而不是eCPMV另外被TLR 7识别。I型干扰素（IFN）的分泌需要TLR 7和包裹的单链RNA（ssRNA）之间的相互作用，这对CPMV的更好疗效至关重要。相同的识别机制也在人外周血单核细胞（PBMC）中起作用。总的来说，这些发现将CPMV免疫治疗功效与分子识别联系起来，为如何开发更有效的病毒颗粒提供了理论基础，强调了多TLR激动剂作为原位癌症疫苗的价值，并突出了I型IFN用于原位疫苗接种的功能重要性。
Cowpea mosaic virus (CPMV), a non-enveloped plant virus, and empty CPMV (eCPMV), a virus-like particle (VLP) composed of CPMV capsid without nucleic acids, are potent in situ cancer vaccines when administered intratumorally (I.T.). However, it is unclear how immune cells recognize these nanoparticles and why they are immunogenic, which was investigated in this study. CPMV generated stronger selective induction of cytokines and chemokines in naïve mouse splenocytes and exhibited more potent anti-tumor efficacy than eCPMV. MyD88 is required for both CPMV- and eCPMV-elicited immune responses. Screening with human embryonic kidney (HEK)-293 cell toll-like receptor (TLR) reporter assays along with experiments in corresponding TLR−/− mice indicated CPMV and eCPMV capsids are recognized by MyD88-dependent TLR2 and TLR4. CPMV but not eCPMV is additionally recognized by TLR7. Secretion of type I interferons (IFNs), which requires the interaction between TLR7 and encapsulated single-stranded RNAs (ssRNAs), is critical to CPMV’s better efficacy. The same recognition mechanisms are also functional in human peripheral blood mononuclear cells (PBMCs). Overall, these findings link CPMV immunotherapy efficacy with molecular recognition, provide rationale for how to develop more potent viral particles, accentuate the value of multi-TLR agonists as in situ cancer vaccines, and highlight the functional importance of type I IFNs for in situ vaccination.
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DOI：
10.1084/jem.20101159
发表时间：
2011-09-26
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Fuertes MB;Kacha AK;Kline J;Woo SR;Kranz DM;Murphy KM;Gajewski TF
通讯作者：
Gajewski TF
影响因子：
7.3
作者：
Kawasaki T;Kawai T
通讯作者：
Kawai T
DOI：
10.1084/jem.20101158
发表时间：
2011-09-26
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Diamond MS;Kinder M;Matsushita H;Mashayekhi M;Dunn GP;Archambault JM;Lee H;Arthur CD;White JM;Kalinke U;Murphy KM;Schreiber RD
通讯作者：
Schreiber RD
影响因子：
6.4
作者：
Albakri, Marwah M.;Veliz, Frank A.;Sieg, Scott F.
通讯作者：
Sieg, Scott F.
影响因子：
4.9
作者：
Hoopes, P. Jack;Wagner, Robert J.;Fiering, Steven N.
通讯作者：
Fiering, Steven N.