A current perspective on cancer immune therapy: step-by-step approach to constructing the magic bullet.
A current perspective on cancer immune therapy: step-by-step approach to constructing the magic bullet.
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DOI：
10.1186/s40169-016-0130-5
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发表时间：
2017-12
影响因子：
10.6
通讯作者：
Sainz B Jr
中科院分区：
文献类型：
--
作者：
D'Errico G;Machado HL;Sainz B Jr
免疫治疗是癌症治疗的新趋势，因为与常规化疗相比，免疫治疗具有选择性、持久的效果，并显示出改善的总生存期和耐受性。尽管有这些积极的结果，免疫疗法仍然远远没有成为对抗癌症的完美灵丹妙药，这主要是因为免疫疗法并不是对所有患者都有效，也不是对所有癌症类型都有效。免疫疗法何时以及如何克服这些障碍？在这篇综述中，我们后退一步，与免疫疗法的先驱并肩而行，以了解今天需要采取哪些步骤来使免疫疗法对所有癌症有效。虽然早期的科学家，如Coley，引发了一种非选择性但有效的抗癌反应，但对选择性的研究将免疫疗法推向了一边，转而支持专注于靶向癌细胞的药物。幸运的是，现代将通过释放制动器或检查点（抗CTLA-4和抗PD-1/PD-L1）来恢复免疫系统在对抗癌症中的重要性。然而，在免疫疗法成为普遍的癌症疗法之前，还有许多障碍需要克服。例如，我们讨论了免疫系统的冗余性和复杂性如何通过在不同的极化状态之间摇摆不定来阻碍肿瘤的消除：一种引发抗癌作用，而另一种促进癌症的生长和侵袭。此外，我们强调免疫系统无法在对抗或修复肿瘤生长之间做出选择。最后，我们结合联合收割机这些概念，提出了一种新的方式来思考免疫系统和免疫耐受性，通过引入两个新的隐喻，“推加速器”和“修理汽车”的隐喻，来解释目前与癌症免疫治疗相关的局限性。
Immunotherapy is the new trend in cancer treatment due to the selectivity, long lasting effects, and demonstrated improved overall survival and tolerance, when compared to patients treated with conventional chemotherapy. Despite these positive results, immunotherapy is still far from becoming the perfect magic bullet to fight cancer, largely due to the facts that immunotherapy is not effective in all patients nor in all cancer types. How and when will immunotherapy overcome these hurdles? In this review we take a step back to walk side by side with the pioneers of immunotherapy in order to understand what steps need to be taken today to make immunotherapy effective across all cancers. While early scientists, such as Coley, elicited an unselective but effective response against cancer, the search for selectivity pushed immunotherapy to the side in favor of drugs focused on targeting cancer cells. Fortunately, the modern era would revive the importance of the immune system in battling cancer by releasing the brakes or checkpoints (anti-CTLA-4 and anti-PD-1/PD-L1) that have been holding the immune system at bay. However, there are still many hurdles to overcome before immunotherapy becomes a universal cancer therapy. For example, we discuss how the redundant and complex nature of the immune system can impede tumor elimination by teeter tottering between different polarization states: one eliciting anti-cancer effects while the other promoting cancer growth and invasion. In addition, we highlight the incapacity of the immune system to choose between a fight or repair action with respect to tumor growth. Finally we combine these concepts to present a new way to think about the immune system and immune tolerance, by introducing two new metaphors, the “push the accelerator” and “repair the car” metaphors, to explain the current limitations associated with cancer immunotherapy.
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DOI：
10.1084/jem.20050915
发表时间：
2005-12-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Casares N;Pequignot MO;Tesniere A;Ghiringhelli F;Roux S;Chaput N;Schmitt E;Hamai A;Hervas-Stubbs S;Obeid M;Coutant F;Métivier D;Pichard E;Aucouturier P;Pierron G;Garrido C;Zitvogel L;Kroemer G
通讯作者：
Kroemer G
影响因子：
4.4
作者：
Ferguson, TA;Herndon, J;Green, DR
通讯作者：
Green, DR
DOI：
10.1073/pnas.76.5.2420
发表时间：
1979-01-01
影响因子：
11.1
作者：
DELEO, AB;JAY, G;OLD, LJ
通讯作者：
OLD, LJ
影响因子：
3.6
作者：
Beaman, Kenneth D.;Jaiswal, Mukesh K.;Gilman-Sachs, Alice
通讯作者：
Gilman-Sachs, Alice
影响因子：
64.8
作者：
BRUNET, JF;DENIZOT, F;GOLSTEIN, P
通讯作者：
GOLSTEIN, P