Abstract

Background

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 with clinicopathological parameters and patient outcome.

Methods

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.

Results

Tumor microenvironment was 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 reduced in cases of PD-L1 (80.76%) expressed primary retinoblastoma, and PD-1 (63.28%) expressed chemoreduced retinoblastoma.

Conclusion

This is the first of its kind study predicting a relevant role of the immune checkpoint markers in 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.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

中文翻译：

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原发性和化学诱导型视网膜母细胞瘤的肿瘤基质微环境中免疫检查点标记物的5P差异表达模式

抽象的

背景

这项研究的目的是确定原发性和化学诱导型视网膜母细胞瘤的肿瘤微环境中的病理发现和免疫检查点标记（PD-1，PD-L1和CTLA-4）的表达，并与临床病理参数和患者预后相关。

方法

前瞻性纳入了262例前瞻性病例，其中144例行了原发性摘除术，118例在摘除前进行了化学疗法/放射疗法（化学性视网膜母细胞瘤）。进行了免疫组织化学，qRT-PCR和蛋白质印迹分析，以评估免疫原性和化学诱导型视网膜母细胞瘤中免疫检查点标记的表达模式。

结果

原发性和化学诱导的视网膜母细胞瘤的肿瘤微环境均不同。PD-1的表达分别在原发性和化学诱导的成视网膜细胞瘤中的29/144（20.13％）和48/118（40.67％）中表达，而PD-L1在46/144（31.94％）和22/118（18.64）中表达。 ％）分别是原发性和化学诱导的视网膜母细胞瘤。两组视网膜母细胞瘤中CTLA-4蛋白的表达模式相似。在多变量分析中，发现大量脉络膜浸润，双侧性和PD-L1表达（p = 0.034）是原发性视网膜母细胞瘤的统计学显着因素，而PD-1表达（p = 0.015）和泡沫巨噬细胞是化学诱导的视网膜母细胞瘤的重要因素。PD-L1（80.76％）表达的原发性视网膜母细胞瘤和PD-1（63。

结论

这是同类研究中的第一个，预测免疫检查点标记在原发性和化学诱导的成视网膜细胞瘤中的相关作用，具有预后意义。这些标记物在两组视网膜母细胞瘤中的差异表达是一个新发现，并且可能是化学耐药性肿瘤的有趣且有益的靶标。

负责研究的法人实体

作者。

资金

尚未收到任何资金。

揭露

所有作者均声明没有利益冲突。