Department of Surgery, Duke University, Durham, NC, USA.
Department of Pathology, Duke University, Durham, NC, USA.
Ann Surg Oncol. 2022 Nov;29(12):7781-7788. doi: 10.1245/s10434-022-12157-0. Epub 2022 Jul 13.
Intraductal papillary mucinous neoplasms (IPMN) are the only radiographically identifiable precursor to pancreatic adenocarcinoma, yet little is known about how these lesions progress to cancer. Inflammation has been associated with dysplastic progression; however, the cause and composition of this inflammation remains poorly characterized. We sought to comprehensively profile immune cell infiltration using parallel spatial transcriptomic and flow cytometric techniques.
Twelve patients with resected IPMN exhibiting both high-grade dysplasia (HGD) and low-grade dysplasia (LGD) were selected for spatial transcriptomics (NanoString GeoMx). Immune (CD45), epithelial (PanCK), and stromal (SMA) compartments were analyzed separately using the GeoMx NGS Pipeline. An additional 11 patients resected for IPMN of varying degrees of dysplasia underwent immunophenotyping using flow cytometry (DURAClone IM).
Spatial transcriptomics revealed that T cells represent the dominant immune cell within IPMN stroma, which was confirmed by flow cytometry (56%). Spatial profiling found that the T-cell infiltrate was significantly higher in regions of LGD compared with HGD (62% vs. 50%, p = 0.038). Macrophages were the only other immune cell type with > 10% abundance, yet conversely, were generally more abundant in regions of HGD compared to LGD (19% vs. 11%, p = 0.058). Correspondingly, immune cells within regions of HGD demonstrated transcriptional upregulation of genes associated with macrophage activity including secretion (CXCL1) and phagocytosis (C1QA, C1S, C4B).
IPMN immune infiltrate is primarily composed of T cells and macrophages. Regions of HGD appear to be relatively deplete of T cells and show a trend toward macrophage enrichment compared with regions of LGD.
导管内乳头状黏液性肿瘤（IPMN）是唯一可在影像学上识别的胰腺癌前体，然而，对于这些病变如何进展为癌症知之甚少。炎症与发育不良进展有关；然而，这种炎症的原因和成分仍未得到很好的描述。我们试图使用平行的空间转录组学和流式细胞术技术全面分析免疫细胞浸润。
选择 12 例经手术切除的同时存在高级别异型增生（HGD）和低级别异型增生（LGD）的 IPMN 患者进行空间转录组学（NanoString GeoMx）分析。使用 GeoMx NGS 管道分别分析免疫（CD45）、上皮（PanCK）和基质（SMA）区室。另外 11 例因不同程度异型增生而切除的 IPMN 患者进行免疫表型分析（流式细胞术 DURAClone IM）。
空间转录组学显示，T 细胞是 IPMN 基质中占主导地位的免疫细胞，这一点得到了流式细胞术的证实（56%）。空间分析发现，LGD 区域的 T 细胞浸润明显高于 HGD 区域（62%比 50%，p=0.038）。巨噬细胞是唯一另一种丰度>10%的免疫细胞类型，但相反，在 HGD 区域比 LGD 区域更为丰富（19%比 11%，p=0.058）。相应地，HGD 区域内的免疫细胞显示与巨噬细胞活性相关的基因转录上调，包括分泌（CXCL1）和吞噬（C1QA、C1S、C4B）。
IPMN 免疫浸润主要由 T 细胞和巨噬细胞组成。HGD 区域似乎相对缺乏 T 细胞，与 LGD 区域相比，巨噬细胞富集的趋势。
