The therapeutic promise of disrupting the PD-1/PD-L1 immune checkpoint in cancer: unleashing the CD8 T cell mediated anti-tumor activity results in significant, unprecedented clinical efficacy in various solid tumors.
The therapeutic promise of disrupting the PD-1/PD-L1 immune checkpoint in cancer: unleashing the CD8 T cell mediated anti-tumor activity results in significant, unprecedented clinical efficacy in various solid tumors.
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破坏癌症中的 PD-1/PD-L1 免疫检查点的治疗前景：释放 CD8 T 细胞介导的抗肿瘤活性，可在各种实体瘤中产生显着的、前所未有的临床疗效。
DOI：
10.1186/s40425-015-0059-z
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发表时间：
2015
影响因子：
10.9
通讯作者：
Romero P
中科院分区：
文献类型：
--
作者：
Romano E;Romero P
免疫检查点在调节T细胞反应的大小和功能方面的作用越来越多地在分子细节上得到理解。抗体介导的共抑制受体阻断已被证明可以恢复慢性病毒感染和癌症中的T细胞功能。后者已成功地转化为治疗癌症的新治疗选择。事实上，在美国、欧洲和日本，阻断CTLA-4或PD-1的单克隆抗体最近已被批准用于治疗转移性黑色素瘤。在这篇评论中，我们总结并透视了最近发表在11月27日（2014年）《自然》杂志上的五封背靠背的信件，这些信件报道了在荷瘤宿主中阻断PD-1/PD-L1通路的不同免疫学和临床方面。值得注意的是，抗pd - l1阻断抗体治疗在包括膀胱癌、肺癌和头颈癌等多种实体肿瘤患者中显示出深刻的临床反应。这五篇同时发表的文章强调了靶向PD-1/PD-L1免疫检查点的巨大治疗潜力，并强调了确定合适的生物标志物以指导其最佳临床应用的必要性。
The role of immune checkpoints in modulating the magnitude as well as the functional profile of T cell responses is increasingly understood in molecular detail. Antibody-mediated blockade of co-inhibitory receptors has been shown to restore T cell function in both chronic viral infections and cancer. The latter has been successfully translated to new therapeutic options in the treatment of cancer. Indeed, monoclonal antibodies blocking either CTLA-4 or PD-1 have recently been approved for the treatment of metastatic melanoma in the United States, Europe and Japan. In this commentary, we summarize and put into perspective five letters recently published back to back in the November 27 (2014) issue of Nature reporting on different immunological and clinical aspects of blockade of the PD-1/PD-L1 pathway in tumor bearing hosts. Notably, treatment with anti-PD-L1 blocking antibody was shown result in profound clinical responses in patients with several solid tumor including bladder, lung and head and neck carcinomas among others. These five simultaneous publications highlight the tremendous therapeutic potential of targeting the PD-1/PD-L1 immune checkpoint and emphasize the need to identify appropriate biomarkers to guide their optimal clinical application.
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DOI：
10.1038/nrc3239
发表时间：
2012-03-22
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Pardoll DM
通讯作者：
Pardoll DM
影响因子：
14.9
作者：
Vita R;Zarebski L;Greenbaum JA;Emami H;Hoof I;Salimi N;Damle R;Sette A;Peters B
通讯作者：
Peters B
影响因子：
11.5
作者：
Harbst, Katja;Staaf, Johan;Jonsson, Goran
通讯作者：
Jonsson, Goran
黑色素瘤肿瘤微环境中PD-L1，IDO和T（REGS）的上调由CD8（+）T细胞驱动。
影响因子：
17.1
作者：
Spranger S;Spaapen RM;Zha Y;Williams J;Meng Y;Ha TT;Gajewski TF
通讯作者：
Gajewski TF
DOI：
10.1056/nejmoa1200694
发表时间：
2012-06-28
期刊：
The New England journal of medicine
影响因子：
--
作者：
Brahmer JR;Tykodi SS;Chow LQ;Hwu WJ;Topalian SL;Hwu P;Drake CG;Camacho LH;Kauh J;Odunsi K;Pitot HC;Hamid O;Bhatia S;Martins R;Eaton K;Chen S;Salay TM;Alaparthy S;Grosso JF;Korman AJ;Parker SM;Agrawal S;Goldberg SM;Pardoll DM;Gupta A;Wigginton JM
通讯作者：
Wigginton JM