The Positive Relationship Between γH2AX and PD-L1 Expression in Lung Squamous Cell Carcinoma
The Positive Relationship Between γH2AX and PD-L1 Expression in Lung Squamous Cell Carcinoma
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DOI：
10.21873/invivo.11221
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发表时间：
2018-01-01
期刊：
影响因子：
2.3
通讯作者：
Sugio, Kenji
中科院分区：
文献类型：
--
作者：
Osoegawa, Atsushi;Hiraishi, Hitomi;Sugio, Kenji
背景/目的：肺鳞状细胞癌通常发生于癌前病变，其中由于致癌物暴露，经常观察到肿瘤抑制基因的改变和随后的染色体不稳定性。这些肿瘤通常具有免疫原性;因此，免疫检查点抑制剂是一种有前途的治疗选择。我们假设肿瘤细胞中的DNA损伤反应诱导免疫反应，从而上调肿瘤细胞上的程序性死亡配体1（PD-L1）表达，进而使其对抗PD-1治疗敏感。患者和方法：在2013年4月至2014年3月期间在我们机构接受手术的41例连续肺鳞状细胞癌患者中进行免疫组织化学分析。结果：分析显示15例患者（37%）PD-L1高表达（p = 0.028）。PD-L1表达与核γ H2AX表达正相关（p = 0.02），这通过免疫荧光染色证实。结论：我们的研究结果表明，核γ H2AX表达与PD-L1表达在肺鳞状细胞癌呈正相关。
Background/Aim: Lung squamous cell carcinoma often arises from precancerous lesions where alterations in tumor suppressor genes and subsequent chromosomal instability are often observed due to carcinogen exposure. These tumors are often immunogenic; as such, immune checkpoint inhibitors are a promising therapeutic option. We hypothesized that the DNA damage response in tumor cells induces an immune response, thereby up-regulating programmed death-ligand 1 (PD-L1) expression on tumor cells, which in turn sensitizes them to anti-PD-1 therapy. Patients and Methods: An immunohistochemical analysis was performed in 41 consecutive lung squamous cell carcinoma patients who underwent surgery at our institution between April 2013 and March 2014. Results: The analysis revealed a high PD-L1 expression in 15 patients (37%) (p=0.028). The PD-L1 expression was positively associated with the nuclear gamma H2AX expression (p=0.02), that was confirmed by immunofluorescent staining. Conclusion: Our findings demonstrate that nuclear gamma H2AX expression is positively associated with the PD-L1 expression in lung squamous cell carcinoma.