PhotoImmunoNanoTherapy reveals an anticancer role for sphingosine kinase 2 and dihydrosphingosine-1-phosphate.
PhotoImmunoNanoTherapy reveals an anticancer role for sphingosine kinase 2 and dihydrosphingosine-1-phosphate.
复制标题
DOI：
10.1021/nn304862b
复制
发表时间：
2013-03-26
期刊：
影响因子：
17.1
通讯作者：
Kester, Mark
中科院分区：
文献类型：
--
作者：
Barth, Brian M.;Shanmugavelandy, Sriram S.;Kaiser, James M.;McGovern, Christopher;Altnoglu, Erhan I.;Haakenson, Jeremy K.;Hengst, Jeremy A.;Gilius, Evan L.;Knupp, Sarah A.;Fox, Todd E.;Smith, Jill P.;Ritty, Timothy M.;Adair, James H.;Kester, Mark
关键词：
肿瘤相关性炎症介导了全身性免疫抑制环境的发展，这是有效治疗癌症的主要障碍。炎症已被证明促进未成熟髓系细胞的全身性扩张，这些未成熟髓系细胞已被证明在癌症实验室模型和癌症患者中发挥免疫抑制活性。因此，正在进行重大努力，以开发减少肿瘤相关炎症和免疫抑制细胞的治疗方法。目前的研究表明，以前描述的一种深层组织成像方式，即利用吲哚青绿负载的磷酸硅酸钙纳米颗粒(ICG-CPSNPs)，可以用作免疫调节剂。ICG-CPSNPs作为光动力治疗的光敏剂的治疗应用被证明通过减少炎症扩张的未成熟髓系细胞来阻止乳腺癌、胰腺癌和转移性骨肉瘤小鼠模型的肿瘤生长。因此，这种治疗方式被称为光免疫纳米疗法。由于磷酸化鞘脂代谢物已被证明具有免疫调节作用，推测光免疫纳米疗法减少未成熟髓系细胞依赖于生物活性的鞘磷脂。在机制上，光免疫纳米治疗诱导了鞘氨醇-1-磷酸和二氢鞘氨醇-1-磷酸依赖的鞘氨醇-1-磷酸的增加。此外，二氢鞘氨醇-1-磷酸被证明选择性地消灭髓系细胞，同时允许发挥抗肿瘤作用的淋巴细胞的扩张。总之，这些发现表明，光免疫纳米治疗，利用新型无毒的治疗药物ICG-CPSNP，可以减少肿瘤相关的炎症和未成熟的髓系细胞，以鞘氨醇激酶2依赖的方式。这些发现进一步定义了二氢鞘氨醇-1-磷酸的一种新的髓系调节作用。光免疫纳米疗法有可能成为治疗具有炎症和免疫抑制表型的癌症的一种革命性疗法。
Tumor-associated inflammation mediates the development of a systemic immunosuppressive milieu that is a major obstacle to effective treatment of cancer. Inflammation has been shown to promote the systemic expansion of immature myeloid cells which have been shown to exert immunosuppressive activity in laboratory models of cancer as well as cancer patients. Consequentially, significant effort is underway toward the development of therapies that decrease tumor-associated inflammation and immunosuppressive cells. The current study demonstrated that a previously described deep tissue imaging modality, which utilized indocyanine green-loaded calcium phosphosilicate nanoparticles (ICG-CPSNPs), could be utilized as an immunoregulatory agent. The theranostic application of ICG-CPSNPs as photosensitizers for photodynamic therapy was shown to block tumor growth in murine models of breast cancer, pancreatic cancer, and metastatic osteosarcoma by decreasing inflammation-expanded immature myeloid cells. Therefore, this therapeutic modality was termed PhotoImmunoNanoTherapy. As phosphorylated sphingolipid metabolites have been shown to have immunomodulatory roles, it was hypothesized that the reduction of immature myeloid cells by PhotoImmunoNanoTherapy was dependent upon bioactive sphingolipids. Mechanistically, PhotoImmunoNanoTherapy induced a sphingosine kinase 2-dependent increase in sphingosine-1-phosphate and dihydrosphingosine-1-phosphate. Furthermore, dihydrosphingosine-1-phosphate was shown to selectively abrogate myeloid lineage cells while concomitantly allowing the expansion of lymphocytes that exerted an antitumor effect. Collectively, these findings revealed that PhotoImmunoNanoTherapy, utilizing the novel nontoxic theranostic agent ICG-CPSNP, can decrease tumor-associated inflammation and immature myeloid cells in a sphingosine kinase 2-dependent manner. These findings further defined a novel myeloid regulatory role for dihydrosphingosine-1-phosphate. PhotoImmunoNanoTherapy holds the potential to be a revolutionary treatment for cancers with inflammatory and immunosuppressive phenotypes.
登录
查看更多内容
影响因子：
10.8
作者：
Kester M;Heakal Y;Fox T;Sharma A;Robertson GP;Morgan TT;Altinoğlu EI;Tabaković A;Parette MR;Rouse SM;Ruiz-Velasco V;Adair JH
通讯作者：
Adair JH
DOI：
10.1126/science.1176709
发表时间：
2009-09-04
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hait NC;Allegood J;Maceyka M;Strub GM;Harikumar KB;Singh SK;Luo C;Marmorstein R;Kordula T;Milstien S;Spiegel S
通讯作者：
Spiegel S
癌症扩增的骨髓源性抑制细胞通过膜结合 TGF-β1 诱导 NK 细胞无反应。
影响因子：
4.4
作者：
Li, Hequan;Han, Yanmei;Cao, Xuetao
通讯作者：
Cao, Xuetao
DOI：
10.1016/j.giec.2009.07.008
发表时间：
2010-01-01
影响因子：
--
作者：
Gross, Seth A;Wolfsen, Herbert C
通讯作者：
Wolfsen, Herbert C
影响因子：
17.1
作者：
Barth BM;Sharma R;Altinoğlu EI;Morgan TT;Shanmugavelandy SS;Kaiser JM;McGovern C;Matters GL;Smith JP;Kester M;Adair JH
通讯作者：
Adair JH