Cancer vaccines: Trafficking of tumor-specific T cells to tumor after therapeutic vaccination.
Cancer vaccines: Trafficking of tumor-specific T cells to tumor after therapeutic vaccination.
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DOI：
10.1016/j.biocel.2014.04.019
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发表时间：
2014-08
影响因子：
4
通讯作者：
Overwijk, Willem W.
中科院分区：
文献类型：
--
作者：
Hailemichael, Yared;Overwijk, Willem W.
癌症疫苗可以诱导肿瘤特异性CD8+T细胞的强大激活，从而摧毁肿瘤。了解癌症疫苗的作用机制对于设计具有更强治疗活性的下一代疫苗至关重要。我们最近报道，短肽在生物可降解性差的不完全弗氏佐剂(IFA)诱导的CD8+T细胞中乳化，这些细胞不定位于肿瘤部位，但聚集在持久的、富含抗原的疫苗接种部位。疫苗接种地点最终成为T细胞墓地，T细胞通过释放细胞因子，包括干扰素-γ(干扰素-γ)，对长期释放的gp100多肽做出反应，进而上调宿主细胞上的Fas配体(Fas L)，导致Fas+T细胞凋亡。逃脱凋亡的T细胞迅速耗尽，记忆力形成差，治疗效果微乎其微。在免疫刺激分子存在的情况下，用水基、短寿命的制剂取代不可生物降解的IFA配方，允许T细胞进入肿瘤，导致它们的消退。在这篇综述中，我们讨论了免疫治疗方法的最新进展，这些方法可以增强疫苗启动的免疫细胞的适合性，并使肿瘤微环境更容易被免疫细胞渗透。
Cancer vaccines can induce robust activation of tumor-specific CD8+ T cells that can destroy tumors. Understanding the mechanism by which cancer vaccines work is essential in designing next-generation vaccines with more potent therapeutic activity. We recently reported that short peptides emulsified in poorly biodegradable, Incomplete Freund’s Adjuvant (IFA) primed CD8+ T cells that did not localize to the tumor site but accumulated at the persisting, antigen-rich vaccination site. The vaccination site eventually became a T cell graveyard where T cells responded to chronically released gp100 peptide by releasing cytokines, including interferon - γ (IFN-γ), which in turn upregulated Fas ligand (FasL) on host cells, causing apoptosis of Fas+ T cells. T cells that escaped apoptosis rapidly became exhausted, memory formation was poor, and therapeutic impact was minimal. Replacing the non-biodegradable IFA-based formulation with water-based, short-lived formulation in the presence of immunostimulatory molecules allowed T cells to traffic to tumors, causing their regression. In this review, we discuss recent advances in immunotherapeutic approaches that could enhance vaccine-primed immune cells fitness and render the tumor microenvironment more accessible for immune cell infiltration.
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DOI：
10.1056/nejmoa1003466
发表时间：
2010-08-19
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hodi FS;O'Day SJ;McDermott DF;Weber RW;Sosman JA;Haanen JB;Gonzalez R;Robert C;Schadendorf D;Hassel JC;Akerley W;van den Eertwegh AJ;Lutzky J;Lorigan P;Vaubel JM;Linette GP;Hogg D;Ottensmeier CH;Lebbé C;Peschel C;Quirt I;Clark JI;Wolchok JD;Weber JS;Tian J;Yellin MJ;Nichol GM;Hoos A;Urba WJ
通讯作者：
Urba WJ
影响因子：
11.2
作者：
Harlin H;Meng Y;Peterson AC;Zha Y;Tretiakova M;Slingluff C;McKee M;Gajewski TF
通讯作者：
Gajewski TF
影响因子：
158.5
作者：
Kantoff, Philip W.;Higano, Celestia S.;Young, J.
通讯作者：
Young, J.
DOI：
10.1158/1078-0432.ccr-10-0712
发表时间：
2010-11-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Peng W;Ye Y;Rabinovich BA;Liu C;Lou Y;Zhang M;Whittington M;Yang Y;Overwijk WW;Lizée G;Hwu P
通讯作者：
Hwu P
影响因子：
64.8
作者：
Mellman, Ira;Coukos, George;Dranoff, Glenn
通讯作者：
Dranoff, Glenn