Department of Biosciences, Jamia Millia Islamia, New Delhi, India.
Department of Ocular Pathology, Dr. R. P. Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, 110029, India.
Cancer Immunol Immunother. 2020 Jun;69(6):1087-1099. doi: 10.1007/s00262-020-02529-4. Epub 2020 Feb 26.
The goal of this study is to identify the pathological findings and expression of immune checkpoint marker (PD-1, PD-L1, and CTLA-4) in the tumor microenvironment of both primary and chemoreduced retinoblastoma and correlate them with clinicopathological parameters and patient outcome.
Total of 262 prospective cases was included prospectively in which 144 cases underwent primary enucleation and 118 cases received chemotherapy/radiotherapy before enucleation (chemoreduced retinoblastoma). Immunohistochemistry, qRT-PCR and western blotting were performed to evaluate the expression pattern of immune checkpoint markers in primary and chemoreduced retinoblastoma.
Tumor microenvironment were different for both primary and chemoreduced retinoblastoma. Expression of PD-1 was found in 29/144 (20.13%) and 48/118 (40.67%) in primary and chemoreduced retinoblastoma, respectively, whereas PD-L1 was expressed in 46/144 (31.94%) and 22/118 (18.64%) in cases of primary and chemoreduced retinoblastoma, respectively. Expression pattern of CTLA-4 protein was similar in both groups of retinoblastoma. On multivariate analysis, massive choroidal invasion, bilaterality and PD-L1 expression (p = 0.034) were found to be statistically significant factors in primary retinoblastoma, whereas PD-1 expression (p = 0.015) and foamy macrophages were significant factors in chemoreduced retinoblastoma. Overall survival was reduced in cases of PD-L1 (80.76%) expressed primary retinoblastoma, and PD-1 (63.28%) expressed chemoreduced retinoblastoma.
This is the first of its kind study predicting a relevant role of the immune checkpoint markers in both groups of primary and chemoreduced retinoblastoma with prognostic significance. Differential expression of these markers in both group of retinoblastoma is a novel finding and might be an interesting and beneficial target for chemoresistant tumors.
本研究旨在确定原发性和化疗后视网膜母细胞瘤肿瘤微环境中免疫检查点标志物（PD-1、PD-L1 和 CTLA-4）的病理表现，并将其与临床病理参数和患者预后相关联。
前瞻性纳入 262 例病例，其中 144 例行初次眼球摘除术，118 例在眼球摘除前行化疗/放疗（化疗后视网膜母细胞瘤）。采用免疫组织化学、qRT-PCR 和 Western blot 检测免疫检查点标志物在原发性和化疗后视网膜母细胞瘤中的表达模式。
原发性和化疗后视网膜母细胞瘤的肿瘤微环境存在差异。PD-1 在原发性和化疗后视网膜母细胞瘤中的表达率分别为 29/144（20.13%）和 48/118（40.67%），PD-L1 的表达率分别为 46/144（31.94%）和 22/118（18.64%）。CTLA-4 蛋白的表达模式在两组视网膜母细胞瘤中相似。多变量分析显示，在原发性视网膜母细胞瘤中，大量脉络膜侵犯、双侧性和 PD-L1 表达（p=0.034）是统计学上显著的因素，而在化疗后视网膜母细胞瘤中，PD-1 表达（p=0.015）和泡沫状巨噬细胞是显著的因素。PD-L1 表达的原发性视网膜母细胞瘤（80.76%）和 PD-1 表达的化疗后视网膜母细胞瘤（63.28%）的总生存率降低。
这是第一项预测免疫检查点标志物在原发性和化疗后视网膜母细胞瘤中具有预后意义的相关作用的研究。这些标志物在两组视网膜母细胞瘤中的差异表达是一个新发现，可能是化学抵抗肿瘤的一个有趣且有益的靶点。
