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ENHANCE-1试验中转移性三阴性乳腺癌患者对艾日布林加派姆单抗反应的空间生物标志物

Spatial biomarkers of response to eribulin plus pembrolizumab in patients with metastatic triple negative breast cancer in the ENHANCE-1 trial.

作者信息

Foong Yee Hoon, Wang Qi, Kearney Matthew, Le Hortense, Guo Hua, Chen Diane, Politis Michelle Garlin, Connelly Courtney F, Kalinsky Kevin, Vanguri Rami S, Connolly Eileen P

机构信息

Division of Precision Medicine, Department of Medicine, Grossman School of Medicine, New York University, New York, NY, 10016, USA.

Department of Radiation Oncology, Columbia University Irving Medical Center, New York, NY, 10032, USA.

出版信息

NPJ Breast Cancer. 2025 Jul 17;11(1):72. doi: 10.1038/s41523-025-00791-2.

DOI:10.1038/s41523-025-00791-2
PMID:40675997
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12271393/
Abstract

ENHANCE-1 was a phase Ib/II study which evaluated eribulin plus pembrolizumab as a treatment for metastatic triple negative breast cancer (mTNBC). All patients had measurable disease and up to 2 prior systemic treatments. We identified 142 patients with available samples and evaluated associations between the pre-treatment tumor-immune microenvironment and response using diagnostic H&Es and multiplexed immunofluorescence with 2 antibody panels. Markers were chosen to evaluate lymphocytes and myeloid cells including: CD4, CD8, FoxP3, CD56, CD20, CD68, CD163, Vimentin, and HLA-DR. While H&E-assessed computational and manual assessments of stromal tumor infiltrating lymphocytes (sTILs) did not associate with response, multiplex immunofluorescence revealed several significant associations. These include enrichment of stromal CD56+ in non-responders and higher stromal CD4 + CD8+ in non-responders in breast samples. Responders exhibited higher stromal macrophage populations CD68 + , CD68+Vimentin + , CD68 + CD163+Vimentin+ as well as higher stromal HLA-DR + . Our results suggest that further studies on immune cell populations other than T-cells as predictive biomarkers for combination therapies in mTNBC are warranted.

摘要

ENHANCE-1是一项Ib/II期研究，评估了艾日布林联合帕博利珠单抗治疗转移性三阴性乳腺癌（mTNBC）的疗效。所有患者均有可测量的病灶，且既往接受过至多2次全身治疗。我们纳入了142例有可用样本的患者，并使用诊断性苏木精和伊红染色（H&E）以及两种抗体组合的多重免疫荧光技术，评估治疗前肿瘤免疫微环境与疗效之间的关联。选择了用于评估淋巴细胞和髓样细胞的标志物，包括：CD4、CD8、FoxP3、CD56、CD20、CD68、CD163、波形蛋白和人类白细胞抗原DR（HLA-DR）。虽然H&E评估的基质肿瘤浸润淋巴细胞（sTILs）的计算机分析和人工评估与疗效无关，但多重免疫荧光显示了几个显著的关联。这些关联包括非应答者中基质CD56+细胞增多，以及乳腺样本中非应答者中基质CD4+CD8+细胞增多。应答者表现出更高的基质巨噬细胞群体，如CD68+、CD68+波形蛋白+、CD68+CD163+波形蛋白+，以及更高的基质HLA-DR+。我们的结果表明，有必要对mTNBC联合治疗的预测生物标志物进行进一步研究，以探究除T细胞以外的免疫细胞群体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d58/12271393/7c5a5e3d5a6a/41523_2025_791_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d58/12271393/538d5e3d808d/41523_2025_791_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d58/12271393/f951383e5e74/41523_2025_791_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d58/12271393/7c5a5e3d5a6a/41523_2025_791_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d58/12271393/538d5e3d808d/41523_2025_791_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d58/12271393/f951383e5e74/41523_2025_791_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d58/12271393/7c5a5e3d5a6a/41523_2025_791_Fig3_HTML.jpg

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本文引用的文献

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Front Immunol. 2024 Jul 9;15:1441820. doi: 10.3389/fimmu.2024.1441820. eCollection 2024.
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A panoptic segmentation dataset and deep-learning approach for explainable scoring of tumor-infiltrating lymphocytes.用于肿瘤浸润淋巴细胞可解释评分的全景分割数据集及深度学习方法。
NPJ Breast Cancer. 2024 Jun 28;10(1):52. doi: 10.1038/s41523-024-00663-1.
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Cancers (Basel). 2024 Jun 11;16(12):2189. doi: 10.3390/cancers16122189.
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CD163 macrophages in the triple-negative breast tumor microenvironment are associated with improved survival in the Women's Circle of Health Study and the Women's Circle of Health Follow-Up Study.三阴性乳腺癌肿瘤微环境中的 CD163 巨噬细胞与妇女健康研究和妇女健康随访研究中的生存改善相关。
Breast Cancer Res. 2024 May 8;26(1):75. doi: 10.1186/s13058-024-01831-8.
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JAMA. 2024 Apr 2;331(13):1135-1144. doi: 10.1001/jama.2024.3056.
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