PO.TB10.06 · 肿瘤生物学

一种评估三阴性乳腺癌免疫微环境异质性预后影响的空间图谱分析方法

A spatial profiling approach to evaluating the prognostic impact of heterogeneity in the triple-negative breast cancer immune microenvironment

编号 803 展板 15 时间 4/19 02:00–05:00 区域 Section 32 主讲 Prerana Sensharma, B Eng;MS

分会场 Spatial Protein Profiling and Multi-Modal Mapping of Tumor and Circulating Ecosystems

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作者与单位 Authors & Affiliations

Prerana Sensharma¹, Huidan Zuo², Melanie Dawe³, Megan Hopkins⁴, Zeynep Baskurt⁵, Osvaldo Espin-Garcia⁵, Philippe L. Bedard⁶, Melanie Spears⁴, Susan J. Done²

¹Medical Biophysics, University of Toronto, Toronto, ON, Canada,²Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada,³Princess Margaret Cancer Center, Toronto, ON, Canada,⁴Ontario Institute for Cancer Research, Toronto, ON, Canada,⁵Department of Biostatistics, Princess Margaret Cancer Center, Toronto, ON, Canada,⁶UHN-Toronto General Hospital, Toronto, ON, Canada

摘要 Abstract

中文摘要

三阴性乳腺癌（TNBC）是以缺乏激素受体且无HER2受体扩增为特征的乳腺癌亚型，是侵袭性最强的乳腺癌亚型。TNBC的靶向治疗仍是一大挑战。非靶向化疗方案一直是长期以来的治疗手段，近来又补充了针对PD-1/PDL1通路的免疫检查点抑制剂（ICIs）。TNBC具有高肿瘤突变负荷、PD-1表达和免疫原性，使其成为免疫治疗的良好候选对象。然而，仍需进一步研究以确定从该治疗中获益最多的个体。免疫细胞浸润的空间模式、免疫细胞与肿瘤细胞及免疫细胞与免疫细胞之间的相互关系等因素，会影响免疫微环境的抗肿瘤反应和ICI应答。对存档患者组织样本进行高重数（high-plex）空间分析——一种丰富但尚未充分利用的肿瘤特征描述资源——一直是难题。然而，利用GeoMx数字空间图谱分析仪（DSP），我们在一组存档的未经治疗（treatment-naïve）TNBC肿瘤队列（n=140）中，对40种免疫标志物的空间免疫异质性进行了定量分析。在免疫浸润的独立间质空间区域（来自140例患者的n=486个区域）中，对识别免疫细胞谱系及亚谱系、激活及耗竭状态的40种免疫标志物的异质性进行了定量。总体免疫细胞浸润较低的肿瘤与较高的空间免疫异质性显著相关。值得注意的是，低免疫浸润还与多种免疫抑制性标志物（其中一些是ICI靶点）的显著更高的空间免疫异质性和总表达相关。这提示免疫抑制在间质微环境（stromal niches）中呈空间局限性分布，而这会影响免疫治疗应答。高空间免疫异质性还与患者生存较差的趋势相关。

查看英文原文 English abstract

Triple-negative breast cancer (TNBC), the breast cancer subtype defined by the absence of hormone receptors and no amplified HER2 receptors, is the most aggressive breast cancer subtype. Targeted treatment remains a challenge with TNBC. Non-targeted chemotherapy regimens have been the longstanding treatment modality, recently supplemented by immune checkpoint inhibitors (ICIs) targeting the PD-1/PDL1 pathway. TNBC's high tumor mutational burden, PD-1 expression, and immunogenicity make it a good candidate for immunotherapy. However, further studies are needed to determine the individuals that benefit most from this treatment. Factors like the spatial patterns of immune cell infiltration, immune-tumour cell and immune-immune cell relationships impact the immune microenvironment's anti-tumour response and ICI response. The high-plex spatial analysis of archival patient tissue samples-an abundant but underutilised resource for tumor characterization-has remained a challenge. However, using the GeoMx Digital Spatial Profiler (DSP), the spatial immune heterogeneity of 40 immune markers were quantified in a cohort of archival treatment-naïve TNBC tumours (n=140). The heterogeneity of 40 immune markers identifying immune cell lineages and sub lineages, activation and exhaustion states was quantified across separate stromal spatial regions of immune infiltration (n=486 from 140 patients). Tumours with overall low immune cell infiltration were significantly associated with higher spatial immune heterogeneity. Notably, low immune infiltration was also associated with a significantly higher spatial immune heterogeneity and total expression of multiple immunosuppressive markers, some of which are ICI targets This suggests that immunosuppression is spatially localized in stromal niches, which would impact immunotherapy response. High spatial immune heterogeneity was also associated with a trend of poorer patient survival.

利益披露 Disclosure

P. Sensharma, None.. H. Zuo, None.. M. Dawe, None.. Z. Baskurt, None.. O. Espin-Garcia, None.. M. Spears, None.. S. J. Done, None.

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