Regulation of cytotoxic T-cell responses by p53 in cancer.
Regulation of cytotoxic T-cell responses by p53 in cancer.
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DOI：
10.21037/tcr.2016.11.76
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发表时间：
2016-12
影响因子：
0.9
通讯作者：
Iwakuma T
中科院分区：
文献类型：
--
作者：
Braun MW;Iwakuma T
肿瘤抑制因子p53的一个有趣的方面是它能够与适应性免疫系统沟通并控制细胞毒性t淋巴细胞（CTL）对癌细胞的反应。野生型p53 （wtp53）通过参与主要组织相容性复合体（MHC） I类抗原递呈途径的蛋白质（例如，与抗原加工相关的转运蛋白1 （TAP1）和内质网氨基肽酶1 （ERAP1)）、凋亡信号受体Fas/APO-1和抑制性免疫检查点程序性死亡配体1 (PD-L1)）与ctl交流。癌细胞中wtp53的存在最终促进了效应ctl诱导的肿瘤细胞死亡。类似地，肿瘤中的wtp53通过抑制PD-L1释放CTL反应，并通过上调Fas/APO-1和MHC i来增强其有效性。鉴于p53在大约50%的人类癌症中发生突变，并影响癌细胞的免疫反应性，大量患者可能受到非功能性p53导致的CTL反应受损的影响。由于p53突变导致的CTL反应减弱可能降低免疫治疗药物的应答率，导致患者预后不良。本文将对p53如何调控细胞介导的癌症适应性免疫反应进行综述。
An intriguing aspect of the tumor suppressor p53 is its ability to communicate to the adaptive immune system and control the cytotoxic T-lymphocyte (CTL) response to cancer cells. Wild-type p53 (wtp53) communicates with CTLs through proteins involved in the major histocompatibility complex (MHC) class I antigen presentation pathway [e.g., transporter associated with antigen processing 1 (TAP1) and endoplasmic reticulum amino peptidase 1 (ERAP1)], the apoptosis signal receptor Fas/APO-1, and the inhibitory immune-checkpoint programmed death-ligand 1 (PD-L1). The presence of wtp53 in cancer cells ultimately promotes effector CTL-induced tumor cell death. Analogously, wtp53 in tumors unleashes the CTL response via inhibition of PD-L1 and enhances their effectiveness by upregulating Fas/APO-1 and MHC I. Given that p53 is mutated in approximately 50% of human cancers and also impacts the immunoreactivity of cancer cells, a significant number of patients can be affected by the impaired CTL response that results from non-functional p53. An attenuated CTL response due to p53 mutations could decrease response rates to immunotherapeutic drugs, leading to poor patient prognoses. This review article will summarize how p53 can regulate the cell-mediated adaptive immune response to cancer.
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DOI：
10.1084/jem.20052271
发表时间：
2006-03-20
期刊：
The Journal of experimental medicine
影响因子：
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作者：
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DOI：
10.1016/j.lungcan.2016.06.016
发表时间：
2016-09
期刊：
Lung cancer (Amsterdam, Netherlands)
影响因子：
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作者：
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