Genomics to immunotherapy of ovarian clear cell carcinoma: Unique opportunities for management.
Genomics to immunotherapy of ovarian clear cell carcinoma: Unique opportunities for management.
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卵巢透明细胞癌从基因组学到免疫治疗：独特的治疗契机
DOI：
10.1016/j.ygyno.2018.09.001
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发表时间：
2018-11
影响因子：
4.7
通讯作者：
Hasegawa K
中科院分区：
文献类型：
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作者：
Oda K;Hamanishi J;Matsuo K;Hasegawa K
卵巢透明细胞癌 (OCCC) 与其他组织学类型的上皮性卵巢癌不同，具有遗传/表观遗传改变、特定的免疫相关分子谱以及与种族和子宫内膜异位症的流行病学关联。这些发现有助于探索 OCCC 的独特且具体的治疗方法。 OCCC 中的两个主要突变基因是 PIK3CA 和 ARID1A，它们经常相互共存。其他基因的改变也会导致 PI3K（例如 PIK3R1 和 PTEN）的激活和染色质重塑复合物（例如 ARID1B 和 SMARKA4）的失调。尽管 OCCC 中焦点拷贝数变异的数量很少，但在染色体 20q13.2（包括 ZNF217）、8q 和 17q 处反复检测到扩增。表达和甲基化谱都强调了氧化应激和炎症调整的重要性。特别是，低甲基化引起的 HNF-1β 上调有助于从无氧糖代谢向有氧糖代谢的转变。此外，HNF-1β 的上调会激活 STAT3 和 NF-κB 信号传导，并通过产生 IL-6 和 IL-8 导致免疫抑制。 PD-1、Tim-3 和 LAG3 表达增加也可能诱导免疫抑制。林奇综合征中发现的错配修复缺陷（微卫星不稳定）肿瘤也会在一些 OCCC 中引起免疫抑制。在最近一项针对经过严格治疗的铂类耐药卵巢癌的 II 期临床试验中，对抗 PD-1 抗体纳武单抗 (nivolumab) 完全缓解的 20 例病例中，有 2 例属于 OCCC 亚型。因此，遗传改变和独特的肿瘤微环境导致的免疫抑制状态可能与 OCCC 对免疫检查点抑制剂的敏感性有关。在这篇综述中，我们从基因组和免疫学的角度重点介绍了 OCCC 的最新更新和进展，探讨了未来的候选治疗方案。
Ovarian clear cell carcinoma (OCCC) is distinctive from other histological types of epithelial ovarian cancer, with genetic/epigenetic alterations, a specific immune-related molecular profile, and epidemiologic associations with ethnicity and endometriosis. These findings allow for the exploration of unique and specific treatments for OCCC. Two major mutated genes in OCCC are PIK3CA and ARID1A, which are frequently coexistent with each other. Other genes' alterations also contribute to activation of the PI3K (e.g. PIK3R1 and PTEN) and dysregulation of the chromatin remodeling complex (e.g. ARID1B, and SMARKA4). Although the number of focal copy number variations is small in OCCC, amplification is recurrently detected at chromosome 20q13.2 (including ZNF217), 8q, and 17q. Both expression and methylation profiling highlight the significance of adjustments to oxidative stress and inflammation. In particular, up-regulation of HNF-1β resulting from hypomethylation contributes to the switch from anaerobic to aerobic glucose metabolism. Additionally, up-regulation of HNF-1β activates STAT3 and NF-κB signaling, and leads to immune suppression via production of IL-6 and IL-8. Immune suppression may also be induced by the increased expression of PD-1, Tim-3 and LAG3. Mismatch repair deficient (microsatellite instable) tumors as found in Lynch syndrome also induce immune suppression in some OCCC. In a recent phase II clinical trial in heavily-treated platinum-resistant ovarian cancer, two out of twenty cases with a complete response to the anti-PD-1 antibody, nivolumab, were OCCC subtypes. Thus, the immune-suppressive state resulting from both genetic alterations and the unique tumor microenvironment may be associated with sensitivity to immune checkpoint inhibitors in OCCC. In this review, we highlight recent update and progress in OCCC from both the genomic and immunologic points of view, addressing the future candidate therapeutic options.
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影响因子：
4.7
作者：
Chan JK;Brady W;Monk BJ;Brown J;Shahin MS;Rose PG;Kim JH;Secord AA;Walker JL;Gershenson DM
通讯作者：
Gershenson DM
影响因子：
11.2
作者：
Dondeti VR;Wubbenhorst B;Lal P;Gordan JD;D'Andrea K;Attiyeh EF;Simon MC;Nathanson KL
通讯作者：
Nathanson KL
影响因子：
8
作者：
Dong, Y.;Richards, J-A E.;Wajapeyee, N.
通讯作者：
Wajapeyee, N.
DOI：
10.1097/igc.0000000000000677
发表时间：
2016-05-01
影响因子：
4.8
作者：
Friedlander, Michael L.;Russell, Kenneth;Voss, Andreas
通讯作者：
Voss, Andreas
影响因子：
82.9
作者：
通讯作者：
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