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Landscape of Immune Checkpoint Inhibition in Carcinosarcoma (MMMT): Analysis of IDO-1, PD-L1 and PD-1.

癌肉瘤 (MMMT) 免疫检查点抑制的景观: IDO-1 、 PD-L1 和 PD-1 分析。

  • 影响因子:1.80
  • DOI:10.1016/j.prp.2020.152847
  • 作者列表:"Hacking S","Chavarria H","Jin C","Perry A","Nasim M
  • 发表时间:2020-01-31
Abstract

BACKGROUND:Carcinosarcoma (CS) or malignant mixed Müllerian tumor (MMMT), is a rare malignant biphasic tumor, which contains both a malignant epithelial and mesenchymal component. That being said, they have an aggressive clinical course. Given that immune checkpoint inhibitors have mustered significant excitement in the oncology world - immunotherapy could offer significant promise to this poor prognostic cancer subtype. A total of 75 carcinosarcoma cases were identified in our institutional database from 2010 to 2019 and immunohistochemistry for PD-L1, PD-1 and IDO-1 was performed. Out of the 75 patients, 65(87 %) demonstrated >1 % PD-1 expression and 50(67 %) expressed >1 % PD-L1 in either the tumoral and immune stromal components. 29 (39 %) cases demonstrated >20 % PD-1 expression and 14 (19 %) cases expressed >20 % PD-L1. 41(55 %) cases demonstrating co-expression of PD-1 and PD-L1. For IDO-1 64 (85 %) patients showed at least >5 %, while 34 (45 %) showed staining above 20 %. 45 patients (60 %) showed co-expression of IDO-1 and PD-L1, while 59 (79 %) patients had co-expression of IDO and PD-1 above 5 and 1 % respectively. Regarding clinicopathologcial features; older patients (> 65) were more likely to express PD-L1 (>1 %) and IDO-1 (>20 %). For tumor size, IDO-1 expression (>5 %), along with PD-1/IDO-1 Co-expression (>1/5 %), was associated with larger tumor size (>5cm). For myometrial invasion, CSs with >50 % invasion were more likely to express IDO-1 (>20 %) and PD-1/IDO-1 (>1/5 %). Ultimately, the effect of IDO-1, PD-1 and PD-L1 on the clinical profile may be less important than its potential use as a immunotherapeutic, where safe and effective corresponding drugs could be used to treat particular patient populations. Future clinical trials are needed to decipher the association between immune check point inhibitor expression and therapeutic response. This is the only way to definitively prove immune checkpoint immunohistochemistry as predictive biomarkers in this cancer subtype.

摘要

背景: 癌肉瘤 (CS) 或恶性混合性苗勒管肿瘤 (MMMT) 是一种罕见的恶性双相肿瘤,同时含有恶性上皮和间质成分。也就是说,他们有一个积极的临床过程。鉴于免疫检查点抑制剂在肿瘤学世界中引起了显著的兴奋 -- 免疫治疗可以为这种预后不良的癌症亚型提供显著的希望。我们的机构数据库中 2010 年至 2019 年共确定了 75 例癌肉瘤病例,并进行了 PD-L1 、 PD-1 和 IDO-1 的免疫组化。75 例患者中,65 例 (87%) 在肿瘤和免疫基质成分中表达> 1% PD-1,50 例 (67%) 表达> 1% PD-L1。29 例 (39%) PD-1 表达> 20%,14 例 (19%) PD-L1 表达> 20%。41 例 (55%) 显示 PD-1 与 PD-L1 共表达。对于 IDO-1,64 例 (85%) 患者显示至少> 5%,而 34 例 (45%) 显示染色在 20% 以上。45 例 (60%) 患者显示 IDO-1 和 PD-L1 共表达,59 例 (79%) 患者 IDO 和 PD-1 共表达分别在 5 和 1% 以上。关于临床病理特征; 老年患者 (> 65) 更可能表达 PD-L1 (>1%) 和 IDO-1 (>20%)。对于肿瘤大小,IDO-1 表达 (>5 )),以及 PD-1/IDO-1 共表达 (>1/5 )) 与肿瘤大小 (> 5厘米) 相关。对于肌层浸润,浸润> 50% 的 CSs 更可能表达 IDO-1 (>20%) 和 PD-1/IDO-1 (>1/5)。最终,IDO-1,PD-1 和 PD-L1 对临床特征的影响可能不如其作为免疫治疗的潜在用途重要,安全有效的相应药物可用于治疗特定患者人群。需要未来的临床试验来破译免疫检查点抑制剂表达与治疗反应之间的关联。这是明确证明免疫检查点免疫组化作为该癌症亚型预测生物标志物的唯一方法。

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