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循环肿瘤细胞中免疫调节分子的表达与头颈部鳞状细胞癌。

Expression of immune-regulatory molecules in circulating tumor cells derived from patients with head and neck squamous cell carcinoma.

机构信息

Department of Otolaryngology-Head and Neck Surgery, Gunma University Graduate School of Medicine, Gunma, Japan.

Department of Otolaryngology-Head and Neck Surgery, Gunma University Graduate School of Medicine, Gunma, Japan.

出版信息

Oral Oncol. 2019 Feb;89:34-39. doi: 10.1016/j.oraloncology.2018.12.002. Epub 2018 Dec 17.

Abstract

OBJECTIVES

Circulating tumor cells (CTCs) are cells that have shed from tumor tissue into the bloodstream, and the detection and characterization of CTCs in head and neck squamous cell carcinoma (HNSCC) still remain a challenge.

MATERIALS AND METHODS

CTCs were isolated from 30 patients with HNSCC with recurrent and/or distant metastasis, via the depletion of CD45-positive cells with magnetic beads and the expression of multiple epithelial markers (CK19, EpCAM, EGFR, and c-Met) was analyzed by RT-qPCR with a low concentration of RNA from the CTC population. We next investigated the expression of the immune-regulatory molecules, PD-L1, PD-L2, and CD47, in CTC-positive patients and the PD-L1 expression in CTCs was compared with that in tumor tissues.

RESULTS

Twenty-four (80.0%) of the 30 patients were positive for at least one epithelial-related gene. Among the 24 CTC-positive patients, 19 (79.2%), 20 (83.3%), and 17 (70.8%) patients were positive for CD47, PD-L1, and PD-L2, respectively. Interestingly, the expression of these three immune-regulatory molecules was positively correlated to each other. As expected, PD-L1 expression in the tumor tissue did not correspond completely with that in the CTCs.

CONCLUSION

Although clinical application and/or characterization of CTCs are still developing, our findings suggest that the CTCs are rapidly becoming a powerful tool in cancer treatments that involve the use of immune checkpoint inhibitors.

摘要

目的

循环肿瘤细胞(CTC)是从肿瘤组织脱落到血液中的细胞,对头颈鳞状细胞癌(HNSCC)中 CTC 的检测和特征分析仍然是一个挑战。

材料和方法

通过用磁性珠去除 CD45 阳性细胞,并通过 RT-qPCR 分析 CTC 群体中低浓度 RNA 表达的多种上皮标志物(CK19、EpCAM、EGFR 和 c-Met),从 30 例具有复发性和/或远处转移的 HNSCC 患者中分离 CTC。接下来,我们研究了 CTC 阳性患者中免疫调节分子 PD-L1、PD-L2 和 CD47 的表达情况,并比较了 CTC 中的 PD-L1 表达与肿瘤组织中的表达。

结果

30 例患者中,有 24 例(80.0%)至少有一种上皮相关基因呈阳性。在 24 例 CTC 阳性患者中,分别有 19 例(79.2%)、20 例(83.3%)和 17 例(70.8%)患者的 CD47、PD-L1 和 PD-L2 呈阳性。有趣的是,这三种免疫调节分子的表达彼此呈正相关。不出所料,肿瘤组织中的 PD-L1 表达与 CTC 中的表达并不完全对应。

结论

尽管 CTC 的临床应用和/或特征分析仍在发展中,但我们的研究结果表明,CTC 正在迅速成为癌症治疗中使用免疫检查点抑制剂的有力工具。

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