Characterization of the Immune Microenvironment in Inflammatory Breast Cancer Using Multiplex Immunofluorescence.

IF 3.5 4区医学 Q3 CELL BIOLOGY

Pathobiology Pub Date : 2023-01-01 Epub Date: 2022-06-15 DOI:10.1159/000524549

Nahla M Badr, Jack L McMurray, Irini Danial, Steven Hayward, Nancy Y Asaad, Moshira M Abd El-Wahed, Asmaa G Abdou, Marwa M Serag El-Dien, Nisha Sharma, Yoshiya Horimoto, Tapan Sircar, Raghavan Vidya, Fiona Hoar, Daniel Rea, J Louise Jones, Andrea Stevens, David Spooner, Reena Merard, Paul Lewis, Kelly John Hunter, Fedor Berditchevski, Abeer M Shaaban

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引用次数: 0

Abstract

Introduction: Inflammatory breast cancer (IBC) is an aggressive form of breast cancer with a poorly characterized immune microenvironment.

Methods: We used a five-colour multiplex immunofluorescence panel, including CD68, CD4, CD8, CD20, and FOXP3 for immune microenvironment profiling in 93 treatment-naïve IBC samples.

Results: Lower grade tumours were characterized by decreased CD4+ cells but increased accumulation of FOXP3+ cells. Increased CD20+ cells correlated with better response to neoadjuvant chemotherapy and increased CD4+ cells infiltration correlated with better overall survival. Pairwise analysis revealed that both ER+ and triple-negative breast cancer were characterized by co-infiltration of CD20 + cells with CD68+ and CD4+ cells, whereas co-infiltration of CD8+ and CD68+ cells was only observed in HER2+ IBC. Co-infiltration of CD20+, CD8+, CD4+, and FOXP3+ cells, and co-existence of CD68+ with FOXP3+ cells correlated with better therapeutic responses, while resistant tumours were characterized by co-accumulation of CD4+, CD8+, FOXP3+, and CD68+ cells and co-expression of CD68+ and CD20+ cells. In a Cox regression model, response to therapy was the most significant factor associated with improved patient survival.

Conclusion: Those results reveal a complex unique pattern of distribution of immune cell subtypes in IBC and provide an important basis for detailed characterization of molecular pathways that govern the formation of IBC immune landscape and potential for immunotherapy.

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利用多重免疫荧光表征炎症性乳腺癌的免疫微环境

引言炎症性乳腺癌（IBC）是一种侵袭性乳腺癌，其免疫微环境特征不明显：方法：我们使用五色多重免疫荧光面板，包括 CD68、CD4、CD8、CD20 和 FOXP3，对 93 例治疗无效的 IBC 样本进行免疫微环境分析：结果：低级别肿瘤的特点是CD4+细胞减少，但FOXP3+细胞聚集增加。CD20+细胞的增加与新辅助化疗反应的改善相关，CD4+细胞浸润的增加与总生存率的改善相关。配对分析显示，ER+和三阴性乳腺癌的特点是CD20+细胞与CD68+和CD4+细胞共同浸润，而只有在HER2+ IBC中才观察到CD8+和CD68+细胞共同浸润。CD20+、CD8+、CD4+和FOXP3+细胞的共同浸润以及CD68+与FOXP3+细胞的共存与较好的治疗反应相关，而耐药肿瘤的特征是CD4+、CD8+、FOXP3+和CD68+细胞的共同聚集以及CD68+和CD20+细胞的共同表达。在Cox回归模型中，治疗反应是与患者生存率改善相关的最重要因素：这些结果揭示了免疫细胞亚型在 IBC 中复杂而独特的分布模式，为详细描述支配 IBC 免疫格局形成的分子通路以及免疫疗法的潜力提供了重要依据。

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

Pathobiology 医学-病理学

CiteScore

8.50

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： ''Pathobiology'' offers a valuable platform for the publication of high-quality original research into the mechanisms underlying human disease. Aiming to serve as a bridge between basic biomedical research and clinical medicine, the journal welcomes articles from scientific areas such as pathology, oncology, anatomy, virology, internal medicine, surgery, cell and molecular biology, and immunology. Published bimonthly, ''Pathobiology'' features original research papers and reviews on translational research. The journal offers the possibility to publish proceedings of meetings dedicated to one particular topic.