Viral nanoparticle vaccines against S100A9 reduce lung tumor seeding and metastasis.
Viral nanoparticle vaccines against S100A9 reduce lung tumor seeding and metastasis.
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DOI：
10.1073/pnas.2221859120
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发表时间：
2023-10-24
影响因子：
11.1
通讯作者：
Steinmetz, Nicole F.
中科院分区：
文献类型：
--
作者：
Chung, Young Hun;Ortega-Rivera, Oscar A.;Volckaert, Britney A.;Jung, Eunkyeong;Zhao, Zhongchao;Steinmetz, Nicole F.
转移仍然是治疗和根除癌症的最严峻挑战之一。S100 A9是炎症的主要调节因子，其表达与癌症患者的不良预后有关。S100 A9在肺中形成转移前小生境，招募癌细胞并促进转移。利用植物病毒和噬菌体纳米技术，我们开发了针对S100 A9的癌症疫苗。治疗显著降低了携带肿瘤的小鼠的肺和血清中的S100 A9水平，从而防止肺转移。疫苗进一步增加免疫刺激性细胞因子的水平并降低免疫抑制性细胞因子。由于S100 A9在多种癌症类型中的流行，我们假设我们的疫苗在预防转移方面可能具有广泛的意义。转移性癌症占所有癌症相关死亡的90%，并且仍然是癌症治疗中最严峻的挑战之一。越来越多的数据表明，S100 A9是炎症的主要调节因子，在癌症进展和转移中起着核心作用，特别是在肺中，S100 A9形成了转移前的小生境。因此，我们开发了一种针对来自植物病毒和病毒样颗粒的S100 A9的疫苗。使用多种肿瘤小鼠模型，我们证明了S100 A9候选疫苗在预防肺内肿瘤种植和转移性疾病生长方面的有效性。所引发的抗体对S100 A9显示出高特异性，而对S100 A家族的另一成员S100 A8没有交叉反应性。当在乳腺癌和黑色素瘤的转移性小鼠模型中进行测试时，疫苗在静脉内激发或手术切除原发性肿瘤后显著减少了肺肿瘤结节。从机制上讲，疫苗降低了肺和血清中S100 A9的水平，从而增加了具有抗肿瘤功能的免疫刺激性细胞因子[（白细胞介素）IL-12和干扰素γ]的表达，同时降低了免疫抑制性细胞因子（IL-10和转化生长因子β）的水平。这也与肺内髓源性抑制细胞群减少相关。这项工作具有广泛的影响，因为S100 A9在多种癌症中过表达，并与癌症患者的预后不良有关。这些数据为开发靶向S100 A9的治疗和疫苗以预防转移奠定了基础。
Metastasis remains one of the toughest challenges in treatment and eradication of cancer. S100A9 is a major regulator of inflammation, and expression is linked with poor prognoses in cancer patients. S100A9 forms a premetastatic niche in lungs recruiting cancer cells and promoting metastasis. Utilizing plant virus and bacteriophage nanotechnologies, we developed a cancer vaccine targeting S100A9. Treatment significantly reduced S100A9 levels within the lungs and sera in tumor-bearing mice protecting from lung metastasis. The vaccines further increased levels of immunostimulatory cytokines and decreased immunosuppressive cytokines. Due to the prevalence of S100A9 in multiple cancer types, we hypothesize that our vaccine could have wide-ranging implications in preventing metastasis. Metastatic cancer accounts for 90% of all cancer-related deaths and continues to be one of the toughest challenges in cancer treatment. A growing body of data indicates that S100A9, a major regulator of inflammation, plays a central role in cancer progression and metastasis, particularly in the lungs, where S100A9 forms a premetastatic niche. Thus, we developed a vaccine against S100A9 derived from plant viruses and virus-like particles. Using multiple tumor mouse models, we demonstrate the effectiveness of the S100A9 vaccine candidates in preventing tumor seeding within the lungs and outgrowth of metastatic disease. The elicited antibodies showed high specificity toward S100A9 without cross-reactivity toward S100A8, another member of the S100A family. When tested in metastatic mouse models of breast cancer and melanoma, the vaccines significantly reduced lung tumor nodules after intravenous challenge or postsurgical removal of the primary tumor. Mechanistically, the vaccines reduce the levels of S100A9 within the lungs and sera, thereby increasing the expression of immunostimulatory cytokines with antitumor function [(interleukin) IL-12 and interferonγ] while reducing levels of immunosuppressive cytokines (IL-10 and transforming growth factorβ). This also correlated with decreased myeloid-derived suppressor cell populations within the lungs. This work has wide-ranging impact, as S100A9 is overexpressed in multiple cancers and linked with poor prognosis in cancer patients. The data presented lay the foundation for the development of therapies and vaccines targeting S100A9 to prevent metastasis.
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HBx 诱导的 S100A9 以 NF-κB 依赖性方式促进肝细胞癌细胞的生长和转移。
影响因子：
9
作者：
Duan L;Wu R;Zhang X;Wang D;You Y;Zhang Y;Zhou L;Chen W
通讯作者：
Chen W
影响因子：
37.8
作者：
Croce K;Gao H;Wang Y;Mooroka T;Sakuma M;Shi C;Sukhova GK;Packard RR;Hogg N;Libby P;Simon DI
通讯作者：
Simon DI
DOI：
10.1002/advs.202101796
发表时间：
2021-11
期刊：
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
影响因子：
--
作者：
Chung YH;Park J;Cai H;Steinmetz NF
通讯作者：
Steinmetz NF
IL-10的髓样细胞免疫调节调节卵巢癌的鼠模型。
影响因子：
7.3
作者：
Hart KM;Byrne KT;Molloy MJ;Usherwood EM;Berwin B
通讯作者：
Berwin B
DOI：
10.1084/jem.20080132
发表时间：
2008-09-29
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Cheng P;Corzo CA;Luetteke N;Yu B;Nagaraj S;Bui MM;Ortiz M;Nacken W;Sorg C;Vogl T;Roth J;Gabrilovich DI
通讯作者：
Gabrilovich DI