Signaling pathway and dysregulation of PD1 and its ligands in lymphoid malignancies.
Signaling pathway and dysregulation of PD1 and its ligands in lymphoid malignancies.
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DOI：
10.1016/j.bbcan.2015.09.002
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发表时间：
2016-01
期刊：
影响因子：
--
通讯作者：
Young KH
中科院分区：
文献类型：
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作者：
Xia Y;Jeffrey Medeiros L;Young KH
肿瘤细胞逃避免疫破坏，至少部分，通过上调抑制信号，以限制效应T细胞的活化。程序性死亡1 （PD-1）是限制t细胞抗肿瘤反应的最关键的共抑制分子之一。PD-1及其配体PD-L1和PD-L2在各种类型的肿瘤以及肿瘤微环境中的反应性细胞中均有过表达。越来越多的证据表明，PD-1途径抑制剂在实体瘤患者中的临床疗效和毒性很小，但这些抑制剂在淋巴细胞恶性肿瘤中的作用研究得很少。在这篇综述中，我们回顾了PD-1通路在大多数常见淋巴细胞恶性肿瘤中的病理作用，并整理了PD-1通路抑制剂临床试验的临床数据。几种抗pd -1方案在复发/难治性霍奇金淋巴瘤、滤泡性淋巴瘤和弥漫性大B细胞淋巴瘤患者中显示出令人鼓舞的治疗效果。需要进一步的进展来促进对抗pd -1治疗在淋巴细胞恶性肿瘤患者中重建抗肿瘤免疫中的作用的更好理解。接下来的试验将探索PD-1通路抑制剂与多种作用机制不同的药物联合使用的临床效果，为患者创造更多的治疗可能性。
Tumor cells evade immune destruction, at least partially, by upregulating inhibitory signals to limit effector T cell activation. Programmed death 1 (PD-1) is one of the most critical co-inhibitory molecules limiting the T-cell antitumor response. PD-1 and its ligands, PD-L1 and PD-L2, are overexpressed by various types of tumors as well as reactive cells in the tumor microenvironment. A growing body of evidence has shown the clinical efficiency and minimal toxicity of PD-1 pathway inhibitors in patients with solid tumors, but the role of these inhibitors in lymphoid malignancies is much less well studied. In this review, we review the pathologic role of the PD-1 pathway in most common lymphoid malignancies and we organize the clinical data from clinical trials of PD-1 pathway inhibitors. Several anti–PD-1 regimens have shown encouraging therapeutic effects in patients with relapsed/refractory Hodgkin lymphoma, follicular lymphoma, and diffuse large B cell lymphoma. Additional progress is needed to foster an improved understanding of the role of anti–PD-1 therapy in reconstituting antitumor immunity in patients with lymphoid malignancies. Upcoming trials will explore the clinical efficiency of combining PD-1 pathway inhibitors and various agents with diverse mechanisms of action and create more therapeutic possibilities for afflicted patients.