Focused ultrasound for immuno-adjuvant treatment of pancreatic cancer: An emerging clinical paradigm in the era of personalized oncotherapy.
Focused ultrasound for immuno-adjuvant treatment of pancreatic cancer: An emerging clinical paradigm in the era of personalized oncotherapy.
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DOI：
10.1080/08830185.2017.1363199
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发表时间：
2017-11-02
影响因子：
5
通讯作者：
Hwang JH
中科院分区：
文献类型：
--
作者：
Maloney E;Khokhlova T;Pillarisetty VG;Schade GR;Repasky EA;Wang YN;Giuliani L;Primavera M;Hwang JH
目前的临床治疗方案，包括许多紧急免疫策略（例如检查点抑制剂），对胰腺导管腺癌（PDA）的破坏性过程几乎没有影响。PDA的临床试验通常采用多模式治疗，并已开始纳入基质靶向治疗，这些治疗在早期报告中显示出有希望的结果。聚焦超声（FUS）是一种这样的治疗方法，它具有独特的装备，可以解决传统癌症治疗的局部和全身局限性，以及PDA的紧急免疫治疗。FUS方法可以非侵入性地产生利用肿瘤的独特癌基因组/蛋白质组特征的机械和/或热效应。FUS治疗PDA的潜在益处包括：1）靶向肿瘤原位乳化成未变性抗原，促进树突状细胞成熟，增加肿瘤内CD 8 +/ T调节细胞比率和CD 8 + T细胞活性; 2）减少肿瘤内缺氧应激; 3）调节肿瘤细胞膜蛋白定位以增强免疫原性; 4）调节局部细胞因子环境朝向Th 1型炎性特征; 5）上调局部化学引诱物; 6）重塑肿瘤基质; 7）外源包装的免疫刺激抗原、基因和治疗药物的局部递送。虽然迄今为止并非所有这些结果都在实验PDA模型中进行了研究，但从其他实体瘤和疾病模型中获得的原理与PDA的最佳FUS方案的设计直接相关。在这篇综述中，我们讨论了当前和紧急免疫治疗的相关局限性，这些局限性可以通过FUS治疗PDA来改善。
Current clinical treatment regimens, including many emergent immune strategies (e.g. checkpoint inhibitors) have done little to affect the devastating course of pancreatic ductal adenocarcinoma (PDA). Clinical trials for PDA often employ multi-modal treatment, and have started to incorporate stromal-targeted therapies, which have shown promising results in early reports. Focused ultrasound (FUS) is one such therapy that is uniquely equipped to address local and systemic limitations of conventional cancer therapies as well as emergent immune therapies for PDA. FUS methods can non-invasively generate mechanical and/or thermal effects that capitalize on the unique oncogenomic/proteomic signature of a tumor. Potential benefits of FUS therapy for PDA include: 1) emulsification of targeted tumor into undenatured antigens in situ, increasing dendritic cell maturation, and increasing intra-tumoral CD8+/ T regulatory cell ratio and CD8+ T cell activity; 2) reduction in intra-tumoral hypoxic stress; 3) modulation of tumor cell membrane protein localization to enhance immunogenicity; 4) modulation of the local cytokine milieu toward a Th1-type inflammatory profile; 5) up-regulation of local chemoattractants; 6) remodeling the tumor stroma; 7) localized delivery of exogenously packaged immune-stimulating antigens, genes and therapeutic drugs. While not all of these results have been studied in experimental PDA models to date, the principles garnered from other solid tumor and disease models have direct relevance to the design of optimal FUS protocols for PDA. In this review, we address the pertinent limitations in current and emergent immune therapies that can be improved with FUS therapy for PDA.
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影响因子：
8.8
作者：
Couvelard, A;O'Toole, D;Turley, H;Leek, R;Sauvanet, A;Degott, C;Ruszniewski, P;Belghiti, J;Harris, AL;Gatter, K;Pezzella, F
通讯作者：
Pezzella, F
影响因子：
11.2
作者：
Barsoum, Ivraym B.;Smallwood, Chelsea A.;Graham, Charles H.
通讯作者：
Graham, Charles H.
影响因子：
11.2
作者：
Chang, Qing;Jurisica, Igor;Hedley, David W.
通讯作者：
Hedley, David W.
影响因子：
2.9
作者：
Canney, Michael S.;Khokhlova, Vera A.;Bessonova, Olga V.;Bailey, Michael R.;Crum, Lawrence A.
通讯作者：
Crum, Lawrence A.
DOI：
10.1084/jem.20101876
发表时间：
2011-03-14
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
De Monte L;Reni M;Tassi E;Clavenna D;Papa I;Recalde H;Braga M;Di Carlo V;Doglioni C;Protti MP
通讯作者：
Protti MP