Reddy Opal L, Shintaku Peter I, Moatamed Neda A
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, BOX 951732, 1P-241 CHS, Los Angeles, CA, 90095-1732, USA.
Diagn Pathol. 2017 Jun 17;12(1):45. doi: 10.1186/s13000-017-0631-6.
The programmed death-1/programmed death-ligand-1 (PD-1/PD-L1) immune regulatory axis has emerged as a promising new target for cancer therapeutics, with lasting responses seen in the treatment of metastatic renal and lung carcinomas, as well as melanomas. As tumor surface expression of PD-L1 has been found to correlate with objective responses to anti-PD-L1 immunotherapies, we investigated the expression of PD-L1 in human cervical tumors and provide an adopted scoring system for the systematic evaluation of PD-L1 staining.
Immunohistochemical staining for PD-L1 expression was performed on a tissue microarray of 101 normal and neoplastic cervical tissues. Neoplastic cores were divided into three groups: squamous cell carcinoma, adenosquamous carcinoma, and endocervical adenocarcinoma. PD-L1 expression was scored based on an adopted scoring system accounting to percentage and intensity of positivity, and results provided alongside available clinical and demographic data.
Overall, PD-L1 was positive in 32 of 93 (34.4%) cervical carcinomas. Subcategorically, PD-L1 was positive in 28 of 74 (37.8%) squamous cell carcinomas, two of seven (28.6%) adenosquamous carcinomas, and two of 12 (16.7%) endocervical adenocarcinomas. It was negative in six benign cervical tissues.
This study shows a significant expression of PD-L1 in 34.4% of cervical carcinomas and no expression of PD-L1 in benign cervical tissues. These findings suggest a role for further investigation of anti-PD-L1/PD-1 immunotherapies in the treatment of PD-L1-positive cervical tumors. In addition, our adopted scoring system will facilitate more systematic correlations between tumor reactivity and response to treatment.
程序性死亡蛋白1/程序性死亡配体1(PD-1/PD-L1)免疫调节轴已成为癌症治疗中一个有前景的新靶点,在转移性肾癌、肺癌以及黑色素瘤的治疗中可见持久疗效。由于已发现肿瘤表面PD-L1表达与抗PD-L1免疫疗法的客观反应相关,我们研究了人宫颈肿瘤中PD-L1的表达情况,并提供了一种用于系统评估PD-L1染色的改良评分系统。
对101例正常和肿瘤性宫颈组织的组织芯片进行PD-L1表达的免疫组化染色。肿瘤核心分为三组:鳞状细胞癌、腺鳞癌和宫颈管腺癌。根据改良评分系统,依据阳性百分比和强度对PD-L1表达进行评分,并将结果与可用的临床和人口统计学数据一起提供。
总体而言,93例宫颈癌中有32例(34.4%)PD-L1呈阳性。具体分类来看,74例鳞状细胞癌中有28例(37.8%)PD-L1呈阳性,7例腺鳞癌中有2例(28.6%),12例宫颈管腺癌中有2例(16.7%)。6例良性宫颈组织中PD-L1呈阴性。
本研究表明34.4%的宫颈癌中有显著的PD-L1表达,而良性宫颈组织中无PD-L1表达。这些发现提示抗PD-L1/PD-1免疫疗法在治疗PD-L1阳性宫颈肿瘤方面值得进一步研究。此外,我们采用的评分系统将有助于更系统地关联肿瘤反应性与治疗反应。