Multi-platform biomarkers of response to an immune checkpoint inhibitor in the neoadjuvant I-SPY 2 trial for early-stage breast cancer.

IF 11.7 1区医学 Q1 CELL BIOLOGY Cell Reports Medicine Pub Date : 2024-11-03 DOI:10.1016/j.xcrm.2024.101799

Michael J Campbell, Denise M Wolf, Christina Yau, Lamorna Brown-Swigart, Julie Wulfkuhle, Isela R Gallagher, Zelos Zhu, Jennifer Bolen, Scott Vandenberg, Clifford Hoyt, Hidetoshi Mori, Alexander Borowsky, Laura Sit, Jane Perlmutter, Smita M Asare, Rita Nanda, Minetta C Liu, Douglas Yee, Angela M DeMichele, Nola M Hylton, Lajos Pusztai, Donald A Berry, Gillian L Hirst, Emanuel F Petricoin, Laura Van't Veer, Laura Esserman

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Abstract

Only a subset of patients with breast cancer responds to immune checkpoint blockade (ICB). To better understand the underlying mechanisms, we analyze pretreatment biopsies from patients in the I-SPY 2 trial who receive neoadjuvant ICB using multiple platforms to profile the tumor microenvironment. A variety of immune cell populations and markers of immune/cytokine signaling associate with pathologic complete response (pCR). Interestingly, these differ by breast cancer receptor subtype. Measures of the spatial distributions of immune cells within the tumor microenvironment, in particular colocalization or close spatial proximity of PD-1⁺ T cells with PD-L1⁺ cells (immune and tumor cells), are significantly associated with response in the overall cohort as well as the in the triple negative (TN) and HR⁺HER2^- subtypes. Our findings indicate that biomarkers associated with immune cell signaling, immune cell densities, and spatial metrics are predictive of neoadjuvant ICB efficacy in breast cancer.

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早期乳腺癌新辅助治疗 I-SPY 2 试验中免疫检查点抑制剂反应的多平台生物标志物。

只有一部分乳腺癌患者对免疫检查点阻断疗法（ICB）有反应。为了更好地了解其潜在机制，我们使用多种平台分析了I-SPY 2试验中接受新辅助ICB的患者的预处理活检组织，以分析肿瘤微环境。各种免疫细胞群和免疫/细胞因子信号标记与病理完全反应（pCR）有关。有趣的是，这些指标因乳腺癌受体亚型而异。对肿瘤微环境中免疫细胞空间分布的测量，特别是 PD-1+ T 细胞与 PD-L1+ 细胞（免疫细胞和肿瘤细胞）的共定位或空间接近性，与总体队列以及三阴性 (TN) 和 HR+HER2- 亚型的反应显著相关。我们的研究结果表明，与免疫细胞信号传导、免疫细胞密度和空间指标相关的生物标志物可预测乳腺癌新辅助 ICB 的疗效。

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

Cell Reports Medicine Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)

CiteScore

15.00

自引率

1.40%

发文量

231

审稿时长

40 days

期刊介绍： Cell Reports Medicine is an esteemed open-access journal by Cell Press that publishes groundbreaking research in translational and clinical biomedical sciences, influencing human health and medicine. Our journal ensures wide visibility and accessibility, reaching scientists and clinicians across various medical disciplines. We publish original research that spans from intriguing human biology concepts to all aspects of clinical work. We encourage submissions that introduce innovative ideas, forging new paths in clinical research and practice. We also welcome studies that provide vital information, enhancing our understanding of current standards of care in diagnosis, treatment, and prognosis. This encompasses translational studies, clinical trials (including long-term follow-ups), genomics, biomarker discovery, and technological advancements that contribute to diagnostics, treatment, and healthcare. Additionally, studies based on vertebrate model organisms are within the scope of the journal, as long as they directly relate to human health and disease.