PO.TB10.06 · 肿瘤生物学

使用CosMx® SMI对TCR和BCR库进行单细胞空间多组学分析，以表征PBMC和肿瘤中的免疫细胞动态

Single cell spatial multiomics of TCR and BCR repertoires using CosMx® SMI to characterize immune cell dynamics in PBMCs and tumors

编号 808 展板 20 时间 4/19 02:00–05:00 区域 Section 32 主讲 Margaret Hoang, PhD

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

Margaret L. Hoang, Rachel Liu, Dan McGuire, Ashley Heck, Kimberly Young, Megan Vandenberg, Claire Williams, Martin Shelton, Prajan Divakar, Patrick Danaher, Erin Piazza, Joseph M. Beechem

Research and Development, Bruker Spatial Biology, Seattle, WA

摘要 Abstract

中文摘要

免疫细胞动态塑造肿瘤对治疗的反应。外周血单个核细胞（PBMCs）提供了适应性免疫的系统性视角，然而传统的免疫测序缺乏空间分辨率，无法将这些发现置于组织结构背景中。肿瘤浸润淋巴细胞（TILs）的高分辨率空间映射揭示了细胞间相互作用，阐明了免疫细胞如何与肿瘤细胞及肿瘤微环境（TME）相互作用以影响免疫治疗结局。我们提出一种使用CosMx空间分子成像（SMI）平台的空间多组学策略，以同时分析PBMCs和肿瘤组织内的T细胞受体（TCR）和B细胞受体（BCR）库。免疫分析纳入了CosMx TCR附加面板，涵盖alpha、beta、gamma和delta链的V、J和恒定区段，以及BCR重链V区和恒定区。这些检测与CosMx全转录组（WTX）和人类免疫肿瘤学64重蛋白面板整合，以对PBMCs进行全面的免疫细胞表征。对肿瘤FFPE切片进行高分辨率亚细胞CosMx SMI成像，结合先进的计算流程，实现了TILs的单细胞空间映射，捕获了TCR/BCR克隆型分布以及免疫细胞与肿瘤细胞和细胞外基质（ECM）成分（包括癌相关成纤维细胞（CAFs）、纤连蛋白（FN1）、alpha-平滑肌肌动蛋白（alpha-SMA））的相互作用。我们揭示了PBMCs和肿瘤中T细胞和B细胞表型的不同模式，包括激活、耗竭和细胞因子信号传导的多组学特征。空间背景揭示了富含T细胞和B细胞的免疫微环境，以及与免疫抑制性ECM信号相关的TIL排斥区域。通过将空间多组学与免疫库分析相结合，该方法揭示了跨系统性和肿瘤区室的关键免疫动态，为生物标志物发现和免疫治疗策略提供了信息。

查看英文原文 English abstract

Immune cell dynamics shape tumor responses to therapy. Peripheral blood mononuclear cells (PBMCs) offer a systemic view of adaptive immunity, yet conventional immune sequencing lacks the spatial resolution to contextualize these findings within tissue architecture. High resolution spatial mapping of tumor-infiltrating lymphocyte (TILs) reveals cell-to-cell interactions, illustrating how immune cells engage with tumor cells and the tumor microenvironment (TME) to influence immunotherapeutic outcomes.We present a spatial multiomics strategy using the CosMx Spatial Molecular Imaging (SMI) platform to simultaneously profile T-cell receptor (TCR) and B-cell receptor (BCR) repertoires within PBMCs and tumor tissues. Immune profiling incorporated the CosMx TCR Add-on panel covering V, J, and constant segments of alpha, beta, gamma, and delta chains, along with BCR heavy chain V and constant region. These assays were integrated with CosMx Whole Transcriptome (WTX) and the Human Immuno-Oncology 64-plex protein panel for comprehensive immune cell characterization in PBMCs. High-resolution subcellular CosMx SMI imaging of tumor FFPE sections, combined with advanced computational pipelines, enabled single cell spatial mapping of TILs, capturing TCR/BCR clonotype distributions and immune cell interactions with tumor cells and the extracellular matrix (ECM) components including cancer-associated fibroblasts (CAFs), fibronectin (FN1), alpha-smooth muscle actin (alpha-SMA).We uncovered distinct patterns of T- and B-cell phenotypes across PBMCs and tumors, including multiomics signatures of activation, exhaustion, and cytokine signaling. Spatial context revealed immune niches enriched for T and B cells, as well as regions of TIL exclusion associated with immunosuppressive ECM signals. By combining spatial multiomics with immune repertoire profiling, this approach uncovers critical immune dynamics across systemic and tumor compartments, informing biomarker discovery and immunotherapy strategies.

利益披露 Disclosure

M. L. Hoang, None.. R. Liu, None.. D. McGuire, None.. A. Heck, None.. K. Young, None.. M. Vandenberg, None.. C. Williams, None.. M. Shelton, None.. P. Divakar, None.. P. Danaher, None.. E. Piazza, None.. J. M. Beechem, None.

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