Checkpoint inhibitors in hematological malignancies.
Checkpoint inhibitors in hematological malignancies.
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DOI：
10.1186/s13045-017-0474-3
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发表时间：
2017-05-08
影响因子：
28.5
通讯作者：
Young KH
中科院分区：
文献类型：
--
作者：
Ok CY;Young KH
PD-1、CTLA-4、LAG-3、TIM-3等抑制分子在免疫功能中起平衡作用。然而，许多癌症利用这些分子来逃避免疫监视。越来越多的数据支持它们的功能在淋巴样肿瘤中失调，包括浆细胞骨髓瘤、骨髓增生异常综合征和急性髓系白血病。在淋巴样肿瘤中，9p24.1 （PD-L1、PD-L2和JAK2位点）的畸变、潜伏的eb病毒感染、PD-L1 3 ' -非翻译区破坏和组成性JAK-STAT通路是诱导PD-L1在淋巴瘤细胞中表达的已知机制。临床试验表明，PD-1阻断是恢复血液学恶性肿瘤，特别是经典霍奇金淋巴瘤的宿主免疫功能的一种有吸引力的方法。许多临床试验正在探索PD-1阻断作为单一疗法或与其他免疫检查点抑制剂联合治疗血液病患者。尽管免疫检查点抑制剂在某些癌症患者中观察到令人印象深刻的临床反应，但并非所有患者都对免疫检查点抑制剂有反应。因此，确定对检查点抑制剂有良好反应的最佳候选人是至关重要的。有几种可能的生物标志物，但尚未达成共识，寻找最佳生物标志物的努力仍在进行中。
Inhibitory molecules such as PD-1, CTLA-4, LAG-3, or TIM-3 play a role to keep a balance in immune function. However, many cancers exploit such molecules to escape immune surveillance. Accumulating data support that their functions are dysregulated in lymphoid neoplasms, including plasma cell myeloma, myelodysplastic syndrome, and acute myeloid leukemia. In lymphoid neoplasms, aberrations in 9p24.1 (PD-L1, PD-L2, and JAK2 locus), latent Epstein-Barr virus infection, PD-L1 3′-untranslated region disruption, and constitutive JAK-STAT pathway are known mechanisms to induce PD-L1 expression in lymphoma cells. Clinical trials demonstrated that PD-1 blockade is an attractive way to restore host’s immune function in hematological malignancies, particularly classical Hodgkin lymphoma. Numerous clinical trials exploring PD-1 blockade as a single therapy or in combination with other immune checkpoint inhibitors in patients with hematologic cancers are under way. Although impressive clinical response is observed with immune checkpoint inhibitors in patients with certain cancers, not all patients respond to immune checkpoint inhibitors. Therefore, to identify best candidates who would have excellent response to checkpoint inhibitors is of utmost importance. Several possible biomarkers are available, but consensus has not been made and pursuit to discover the best biomarker is ongoing.