PD-1/PD-L blockade in gastrointestinal cancers: lessons learned and the road toward precision immunotherapy.
PD-1/PD-L blockade in gastrointestinal cancers: lessons learned and the road toward precision immunotherapy.
复制标题
DOI：
10.1186/s13045-017-0511-2
复制
发表时间：
2017-08-03
影响因子：
28.5
通讯作者：
Zhao H
中科院分区：
文献类型：
--
作者：
Long J;Lin J;Wang A;Wu L;Zheng Y;Yang X;Wan X;Xu H;Chen S;Zhao H
胃肠道（GI）恶性肿瘤是世界范围内最常见的肿瘤，其发病率和死亡率都在不断上升。尽管手术切除、化疗、放疗和分子靶向治疗使胃肠道肿瘤患者的治疗取得了重大进展，但总体生存率仍然很低。因此，必须确定替代策略以改善患者的预后。在肿瘤微环境中，肿瘤细胞可以通过PD-1和PD-L的相互作用逃避宿主免疫应答，抑制T细胞和肿瘤浸润淋巴细胞的功能，同时增加免疫抑制性T调节细胞的功能。使用抗pd -1/PD-L阻断使免疫系统重编程能够有效地识别和杀死肿瘤细胞。近年来，PD-1/PD-L阻断在多种肿瘤中的疗效得到证实，有望成为肿瘤的泛免疫疗法。在这里，我们回顾了肿瘤中PD-1/PD-L失调的信号通路，总结了目前胃肠道恶性肿瘤中PD-1/PD-L抑制剂的临床数据，并讨论了与PD-1/PD-L阻断相关的精确免疫治疗之路。PD-1/PD-L抑制剂的初步数据令人鼓舞，PD-1/PD-L抑制剂的精确免疫治疗将成为胃肠道肿瘤治疗的一种可行和关键的临床策略。
Gastrointestinal (GI) malignancies are the most prevalent tumors worldwide, with increasing incidence and mortality. Although surgical resection, chemotherapy, radiotherapy, and molecular targeted therapy have led to significant advances in the treatment of GI cancer patients, overall survival is still low. Therefore, alternative strategies must be identified to improve patient outcomes. In the tumor microenvironment, tumor cells can escape the host immune response through the interaction of PD-1 and PD-L, which inhibits the function of T cells and tumor-infiltrating lymphocytes while increasing the function of immunosuppressive T regulatory cells. The use of an anti-PD-1/PD-L blockade enables reprogramming of the immune system to efficiently identify and kill tumor cells. In recent years, the efficacy of PD-1/PD-L blockade has been demonstrated in many tumors, and this treatment is expected to be a pan-immunotherapy for tumors. Here, we review the signaling pathway underlying the dysregulation of PD-1/PD-L in tumors, summarize the current clinical data for PD-1/PD-L inhibitors in GI malignancies, and discuss road toward precision immunotherapy in relation to PD-1/PD-L blockade. The preliminary data for PD-1/PD-L inhibitors are encouraging, and the precision immunotherapy of PD-1/PD-L inhibitors will be a viable and pivotal clinical strategy for GI cancer therapy.
登录
查看更多内容
PD-1检查点途径的分子和生化方面。
DOI：
10.1056/nejmra1514296
发表时间：
2016-11-03
期刊：
The New England journal of medicine
影响因子：
--
作者：
Boussiotis VA
通讯作者：
Boussiotis VA
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
影响因子：
11.5
作者：
Champiat, Stephane;Dercle, Laurent;Ferte, Charles
通讯作者：
Ferte, Charles
影响因子：
8
作者：
Ahmad, Ali;Reha, Jeffrey;Katz, Steven C.
通讯作者：
Katz, Steven C.
影响因子：
15.9
作者：
Deng, Liufu;Liang, Hua;Fu, Yang-Xin
通讯作者：
Fu, Yang-Xin