Ocular Pathology, All India Institute of Medical Sciences, New Delhi, Delhi, India.
Biosciences, Jamia Millia Islamia, New Delhi, Delhi, India.
Br J Ophthalmol. 2021 Jan;105(1):48-56. doi: 10.1136/bjophthalmol-2019-315490. Epub 2020 Apr 10.
Immune checkpoint blockade strategies have gained attention in the treatment/prognosis of cancers by targeting the programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway alone or in combination with cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) blockade and are currently in clinical trials. The present study investigated the expression of the PD-1, PD-L1, CTLA-4, CD4 and CD8 proteins and their prognostic value in the tumour microenvironment of sebaceous gland carcinoma (SGC).
The expression levels of PD-1, PD-L1, CTLA-4, CD4 and CD8 proteins were assessed in 52 cases of SGC by immunohistochemistry and validated by western blotting. mRNA expression was measured by quantitative real-time PCR. Kaplan-Meier curves and Cox proportional hazard models were used to analyse the correlation of protein expression with clinicopathological parameters and disease-free survival.
The expression of PD-L1 was found to be higher in tumour cells than in stromal cells. In univariate analysis, the expression of PD-1 in tumour-infiltrating lymphocytes (tPD-1) and PD-L1 in tumour cells was associated with reduced disease-free survival, whereas PD-L1 expression in stromal lymphocyte infiltration (sPD-L1) was associated with the increased survival of patients (p<0.05). However, by multivariate analysis, the expression of tPD-1 was found to be an independent prognostic factor for poor survival.
Our study highlights the prognostic outcome of PD-1 and PD-L1 protein expression in cells of tumour-stromal compartments. These results indicate that the PD-1/PD-L1 pathway mediates important interactions within the tumour microenvironment in SGC.
免疫检查点阻断策略通过单独靶向程序性死亡-1（PD-1）/程序性死亡配体 1（PD-L1）途径或与细胞毒性 T 淋巴细胞相关抗原 4（CTLA-4）阻断联合，在癌症的治疗/预后方面受到关注，目前正在临床试验中。本研究调查了 PD-1、PD-L1、CTLA-4、CD4 和 CD8 蛋白在皮脂腺癌（SGC）肿瘤微环境中的表达及其预后价值。
通过免疫组织化学评估 52 例 SGC 中 PD-1、PD-L1、CTLA-4、CD4 和 CD8 蛋白的表达水平，并通过 Western blot 进行验证。通过实时定量 PCR 测量 mRNA 表达。使用 Kaplan-Meier 曲线和 Cox 比例风险模型分析蛋白表达与临床病理参数和无病生存的相关性。
发现肿瘤细胞中 PD-L1 的表达高于基质细胞。在单因素分析中，肿瘤浸润淋巴细胞（tPD-1）中 PD-1 的表达和肿瘤细胞中 PD-L1 的表达与无病生存时间缩短相关，而基质淋巴细胞浸润中 PD-L1 的表达（sPD-L1）与患者生存时间的延长相关（p<0.05）。然而，通过多因素分析，发现 tPD-1 的表达是生存不良的独立预后因素。
本研究强调了 PD-1 和 PD-L1 蛋白在肿瘤-基质细胞区室中的表达的预后结果。这些结果表明，PD-1/PD-L1 途径在 SGC 肿瘤微环境中介导重要的相互作用。
