Immune profiling of mouse lung adenocarcinoma paraffin tissues using multiplex immunofluorescence panel: a pilot study.

IF 2.7 Q3 MEDICINE, RESEARCH & EXPERIMENTAL
Jie Zhai, Auriole Tamegnon, Mei Jiang, Renganayaki Krishna Pandurengan, Edwin Roger Parra
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Abstract

Background: Immune profiling has become an important tool for identifying predictive, prognostic and response biomarkers for immune checkpoint inhibitors from tumor microenvironment (TME). We aimed to build a multiplex immunofluorescence (mIF) panel to apply to formalin-fixed and paraffin-embedded tissues in mice tumors and to explore the programmed cell death protein 1/ programmed cell death 1 ligand 1 (PD-1/PD-L1) axis.

Results: An automated eight-color mIF panel was evaluated to study the TME using seven antibodies, including cytokeratin 19, CD3e, CD8a, CD4, PD-1, PD-L1, F4-80 and DAPI, then was applied in six mice lung adenocarcinoma samples. Cell phenotypes were quantified by software to explore the co-localization and spatial distribution between immune cells within the TME. This mice panel was successfully optimized and applied to a small cohort of mice lung adenocarcinoma cases. Image analysis showed a sparse degree of immune cell expression pattern in this cohort. From the spatial analysis we found that T cells and macrophages expressing PD-L1 were close to the malignant cells and other immune cells.

Conclusions: Comprehensive immune profiling using mIF in translational studies improves our ability to correlate the PD-1/PD-L1 axis and spatial distribution of lymphocytes and macrophages in mouse lung cancer cells to provide new cues for immunotherapy, that can be translated to human tumors for cancer intervention.

利用多重免疫荧光板对小鼠肺腺癌石蜡组织进行免疫分析:一项试验性研究。
背景:免疫分析已成为从肿瘤微环境(TME)中鉴定免疫检查点抑制剂的预测、预后和反应生物标志物的重要工具。我们的目的是建立一个多重免疫荧光(mIF)面板,应用于福尔马林固定和石蜡包埋的小鼠肿瘤组织,并探索程序性细胞死亡蛋白1/程序性细胞死亡1配体1(PD-1/PD-L1)轴:使用七种抗体(包括细胞角蛋白19、CD3e、CD8a、CD4、PD-1、PD-L1、F4-80和DAPI)评估了研究TME的自动八色mIF面板,然后将其应用于6个小鼠肺腺癌样本。通过软件对细胞表型进行量化,以探索免疫细胞在TME内的共定位和空间分布。该小鼠面板已成功优化并应用于小鼠肺腺癌病例群。图像分析表明,该组小鼠的免疫细胞表达模式稀疏。通过空间分析,我们发现表达 PD-L1 的 T 细胞和巨噬细胞靠近恶性细胞和其他免疫细胞:结论:在转化研究中使用 mIF 进行全面的免疫分析,提高了我们将 PD-1/PD-L1 轴与小鼠肺癌细胞中淋巴细胞和巨噬细胞的空间分布相关联的能力,为免疫疗法提供了新的线索,并可转化为人类肿瘤的癌症干预措施。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
4.40
自引率
0.00%
发文量
32
审稿时长
8 weeks
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