David G. Cogan Ophthalmic Pathology Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, USA; Division of Ophthalmic Plastic and Reconstructive Surgery, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, USA.
David G. Cogan Ophthalmic Pathology Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, USA.
Am J Ophthalmol. 2019 Apr;200:226-241. doi: 10.1016/j.ajo.2018.12.020. Epub 2019 Jan 8.
Novel cancer immunotherapies, called immune checkpoint inhibitors, have demonstrated clinical efficacy in the treatment of squamous cell carcinomas of the head and neck. Tissue expression of programmed cell death 1 ligand 1 (PD-L1) and programmed cell death 1 ligand 2 (PD-L2) has been shown to predict tumor response to these drugs. We examine the expression of prognostic immune biomarkers, PD-L1 and PD-L2, in invasive ocular surface squamous neoplasia.
Retrospective case series.
Eighteen cases of ocular surface or ocular adnexal invasive squamous cell carcinomas were identified in pathology case files of the Massachusetts General Hospital/Massachusetts Eye and Ear Infirmary and at the Wills Eye Hospital accessioned between January 1, 2014 and January 1, 2017. Immunohistochemical staining for PD-L1, PD-L2, CD8, and p16 was performed and graded in a standardized fashion.
PD-L1 and PD-L2 were expressed on tumor cells to varying degrees, and also on some stromal cells and endothelial cells. Stromal and endothelial cell expression was also seen in control conjunctival specimens. Tumor expression of PD-L1 and PD-L2 was present on the cell membranes. All 18 (100%) of the tumors expressed PD-L1: 7 (39%) expressed a high level, 3 (17%) expressed a medium level, and 8 (44%) expressed a low level. Only 9 (50%) tumors expressed PD-L2 and it was at a low level. The expression of PD-L1 in tumor cells correlated with the presence of CD8-positive cytotoxic T lymphocytes among tumor cells (P < .01) and with the presence of CD8-positive cells in the surrounding stroma (P = .04).
A subset of ocular invasive conjunctival squamous carcinomas express high levels of PD-L1 and CD8 and therefore may respond therapeutically to immune checkpoint inhibition.
新型癌症免疫疗法，称为免疫检查点抑制剂，在治疗头颈部鳞状细胞癌方面已显示出临床疗效。程序性细胞死亡蛋白 1 配体 1（PD-L1）和程序性细胞死亡蛋白 1 配体 2（PD-L2）的组织表达已被证明可预测这些药物对肿瘤的反应。我们检查了侵袭性眼表鳞状肿瘤中预后免疫生物标志物 PD-L1 和 PD-L2 的表达。
回顾性病例系列。
在马萨诸塞州总医院/马萨诸塞州眼耳医院和威尔斯眼医院的病理病例档案中，确定了 18 例眼表面或眼附属器侵袭性鳞状细胞癌病例，这些病例于 2014 年 1 月 1 日至 2017 年 1 月 1 日期间就诊。以标准化方式进行 PD-L1、PD-L2、CD8 和 p16 的免疫组织化学染色和分级。
PD-L1 和 PD-L2 在肿瘤细胞上以不同程度表达，也在一些基质细胞和内皮细胞上表达。在对照结膜标本中也观察到基质和内皮细胞表达。肿瘤细胞膜上表达 PD-L1 和 PD-L2。所有 18 例（100%）肿瘤均表达 PD-L1：7 例（39%）表达高水平，3 例（17%）表达中水平，8 例（44%）表达低水平。仅 9 例（50%）肿瘤表达 PD-L2，且水平较低。肿瘤细胞中 PD-L1 的表达与肿瘤细胞中 CD8 阳性细胞毒性 T 淋巴细胞的存在相关（P <.01），与周围基质中 CD8 阳性细胞的存在相关（P =.04）。
一部分眼侵袭性结膜鳞状细胞癌表达高水平的 PD-L1 和 CD8，因此可能对免疫检查点抑制治疗有反应。
