胰腺导管腺癌（PDAC）是最具侵袭性的癌症之一，其特点是高度刚性和免疫抑制的肿瘤微环境（TME）。已知广泛的细胞相互作用在免疫逃避、化疗耐药和不良预后中发挥关键作用。在这里，我们使用空间转录组学、scRNA-seq 和bulk RNA-seq 数据集来增强从每个数据集获得的见解，以破译 TME 中的细胞通信。样品的单细胞和空间转录组学特征揭示了 PDAC 样品中复杂的串扰。我们发现肿瘤相关巨噬细胞（TAM）是 PDAC 微环境调节的核心细胞类型。它们与癌细胞和肿瘤抑制免疫细胞共定位，并发挥作用以提供免疫抑制环境。与健康样本相比，LGALS9 基因在 PDAC 肿瘤样本中表达上调，在 TAM 中也发现与癌症样本中的肿瘤抑制免疫细胞相比表达上调。此外，LGALS9 被发现是 TAM 与其他细胞之间串扰的主要成分。 P4HB基因的广泛表达及其与LGALS9的相互作用也值得注意。我们的研究结果表明 TAM 通过 LGALS9 发挥深远作用，及其与 P4HB 的相互作用，应考虑将其作为 PDAC 联合免疫疗法的靶标进行进一步阐明。© 2023。作者。

Pancreatic ductal adenocarcinoma (PDAC) is one the most aggressive cancers and characterized by a highly rigid and immunosuppressive tumor microenvironment (TME). The extensive cellular interactions are known to play key roles in the immune evasion, chemoresistance, and poor prognosis. Here, we used the spatial transcriptomics, scRNA-seq, and bulk RNA-seq datasets to enhance the insights obtained from each to decipher the cellular communication in the TME. The complex crosstalk in PDAC samples was revealed by the single-cell and spatial transcriptomics profiles of the samples. We show that tumor-associated macrophages (TAMs) are the central cell types in the regulation of microenvironment in PDAC. They colocalize with the cancer cells and tumor-suppressor immune cells and take roles to provide an immunosuppressive environment. LGALS9 gene which is upregulated in PDAC tumor samples in comparison to healthy samples was also found to be upregulated in TAMs compared to tumor-suppressor immune cells in cancer samples. Additionally, LGALS9 was found to be the primary component in the crosstalk between TAMs and the other cells. The widespread expression of P4HB gene and its interaction with LGALS9 was also notable. Our findings point to a profound role of TAMs via LGALS9 and its interaction with P4HB that should be considered for further elucidation as target in the combinatory immunotherapies for PDAC.© 2023. The Author(s).