基于检查点的免疫疗法在大部分胰腺癌患者中无法引起响应。在我们的研究中，我们旨在确定一个新型免疫检查点分子V-set Ig domain-containing 4 (VSIG4)在胰腺导管腺癌（PDAC）中的作用。在线数据集和组织微阵列（TMA）被用于分析PDAC中VSIG4的表达水平及其与临床参数的相关性。CCK8、Transwell实验和创面愈合实验被应用于探索VSIG4在 vitro 中的功能。皮下、原位异种移植和肝转移模型被建立来探索VSIG4在 vivo 中的功能。TMA分析和趋化实验被进行来揭示VSIG4对免疫浸润的影响。组蛋白酰转移酶（HAT）抑制剂和si-RNA被应用于研究调节VSIG4表达的因素。在TCGA、GEO、HPA数据集和我们的TMA中，VSIG4的mRNA和蛋白水平在PDAC中高于正常胰腺。VSIG4与肿瘤大小、T分类和肝转移呈正相关。表达更高的VSIG4的患者与较差的预后有关。VSIG4的沉默削弱了胰腺癌细胞在 vitro 和 in vivo 中的增殖和迁移能力。生物信息学研究显示，PDAC中VSIG4与嗜中性粒细胞和肿瘤相关巨噬细胞（TAMs）的浸润呈正相关，并抑制细胞因子的分泌。根据我们的TMA面板，高表达的VSIG4与CD8+T细胞的浸润较少有关。趋化实验还显示，VSIG4的沉默增加了总T细胞和CD8+ T细胞的招募量。HAT抑制剂和STAT1的沉默导致VSIG4的表达减少。我们的数据表明，VSIG4有助于细胞增殖、迁移和抵抗免疫攻击，因此被确定为具有良好预后价值的PDAC治疗的有希望的靶点。©2023作者。

Checkpoint-based immunotherapy has failed to elicit responses in the majority of patients with pancreatic cancer. In our study, we aimed to identify the role of a novel immune checkpoint molecule V-set Ig domain-containing 4 (VSIG4) in pancreatic ductal adenocarcinoma (PDAC).Online datasets and tissue microarray (TMA) were utilized to analyze the expression level of VSIG4 and its correlation with clinical parameters in PDAC. CCK8, transwell assay and wound healing assay were applied to explore the function of VSIG4 in vitro. Subcutaneous, orthotopic xenograft and liver metastasis model was established to explore the function of VSIG4 in vivo. TMA analysis and chemotaxis assay were conducted to uncover the effect of VSIG4 on immune infiltration. Histone acetyltransferase (HAT) inhibitors and si-RNA were applied to investigate factors that regulate the expression of VSIG4.Both mRNA and protein levels of VSIG4 were higher in PDAC than normal pancreas in TCGA, GEO, HPA datasets and our TMA. VSIG4 showed positive correlations with tumor size, T classification and liver metastasis. Patients with higher VSIG4 expression were related to poorer prognosis. VSIG4 knockdown impaired the proliferation and migration ability of pancreatic cancer cells both in vitro and in vivo. Bioinformatics study showed positive correlation between VSIG4 and infiltration of neutrophil and tumor-associated macrophages (TAMs) in PDAC, and it inhibited the secretion of cytokines. According to our TMA panel, high expression of VSIG4 was correlated with fewer infiltration of CD8+ T cells. Chemotaxis assay also showed knockdown of VSIG4 increased the recruitment of total T cells and CD8+ T cells. HAT inhibitors and knockdown of STAT1 led to decreased expression of VSIG4.Our data indicate that VSIG4 contributes to cell proliferation, migration and resistance to immune attack, thus identified as a promising target for PDAC treatment with good prognostic value.© 2023. The Author(s).