Oncogenesis and progression of pancreatic ductal adenocarcinoma (PDAC) is driven by complex interactions between the neoplastic component and the tumor microenvironment (TME), which includes immune, stromal, and parenchymal cells. In particular, most PDACs are characterized by a hypovascular and hypoxic environment that alters tumor cell behavior and limits the efficacy of chemotherapy and immunotherapy. Characterization of the spatial features of the vascular niche could advance our understanding of inter- and intra-tumoral heterogeneity in PDAC. Here, we investigated the vascular microenvironment of PDAC by applying imaging mass cytometry using a 26-antibody panel on 35 regions of interest (ROIs) across 9 patients, capturing over 140,000 single cells. The approach distinguished major cell types, including multiple populations of lymphoid and myeloid cells, endocrine cells, ductal cells, stromal cells, and endothelial cells. Evaluation of cellular neighborhoods identified 10 distinct spatial domains, including multiple immune and tumor-enriched environments as well as the vascular niche. Focused analysis revealed differential interactions between immune populations and the vasculature and identified distinct spatial domains wherein tumor cell proliferation occurs. Importantly, the vascular niche was closely associated with a population of CD44-expressing macrophages enriched for a pro-angiogenic gene signature. Together, this study provides insights into the spatial heterogeneity of PDAC and suggests a role for CD44-expressing macrophages in shaping the vascular niche.

中文翻译：

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多重成像质谱流式分析表征胰腺癌的血管生态位

胰腺导管腺癌 (PDAC) 的肿瘤发生和进展是由肿瘤成分与肿瘤微环境 (TME)（包括免疫细胞、基质细胞和实质细胞）之间复杂的相互作用驱动的。特别是，大多数 PDAC 的特点是血管不足和缺氧环境，这会改变肿瘤细胞的行为并限制化疗和免疫治疗的疗效。血管生态位空间特征的表征可以促进我们对 PDAC 肿瘤间和肿瘤内异质性的理解。在这里，我们通过使用 26 抗体面板对 9 名患者的 35 个感兴趣区域 (ROI) 应用成像质量流式细胞仪，研究了 PDAC 的血管微环境，捕获了超过 140,000 个单细胞。该方法区分了主要细胞类型，包括多种淋巴和骨髓细胞、内分泌细胞、导管细胞、基质细胞和内皮细胞。对细胞邻域的评估确定了 10 个不同的空间域，包括多种免疫和肿瘤丰富的环境以及血管生态位。集中分析揭示了免疫群体与脉管系统之间的差异相互作用，并确定了肿瘤细胞增殖发生的不同空间域。重要的是，血管生态位与富含促血管生成基因特征的表达 CD44 的巨噬细胞群密切相关。总之，这项研究提供了对 PDAC 空间异质性的见解，并表明表达 CD44 的巨噬细胞在塑造血管生态位中的作用。