SIGLEC15在肝细胞癌（HCC）中的功能作用尚不清楚，最近发现SIGLEC15是一种与抑制性B7家族成员结构相似的免疫抑制剂。在公共数据库中探索了 HCC 中的 SIGLEC15 表达，并通过 PCR 分析进一步检查。通过免疫组织化学检查 HCC 样本中的 SIGLEC15 和 PD-L1 表达模式。在HCC细胞系中敲低或过表达SIGLEC15表达，并使用CCK8测试来检查细胞体外增殖能力。分别在免疫缺陷和免疫功能正常的小鼠中检查 SIGLEC15 表达对肿瘤生长的影响。通过 HCC 细胞系和 Jurkat 细胞的共培养系统、肿瘤浸润免疫细胞的流式细胞术分析以及进一步的测序分析来研究 SIGLEC15 如何在体外和体内影响 T 细胞。我们发现 SIGLEC15 在 HCC 肿瘤组织中增加，并且与 HCC 样本中的 PD-L1 呈负相关。体外和体内模型表明，抑制 SIGLEC15 并不直接影响肿瘤增殖。然而，SIGLEC15 可以在免疫能力强的小鼠模型中促进 HCC 免疫逃避。 Siglec15 的敲除可以抑制肿瘤生长并重振 CD8 T 细胞的细胞毒性。抗SIGLEC15治疗可以有效抑制有或没有单核吞噬细胞缺失的小鼠模型中的肿瘤生长。治疗小鼠肿瘤的批量和单细胞 RNA 测序数据表明 SIGLEC15 可以干扰 CD8 T 细胞活力并诱导细胞凋亡。总之，SIGLEC15 在 HCC 中与 PD-L1 呈负相关，主要通过抑制 CD8 T 细胞活力和细胞毒性来促进 HCC 免疫逃避。© 2024 作者。经泰勒许可出版

Functional roles of SIGLEC15 in hepatocellular carcinoma (HCC) were not clear, which was recently found to be an immune inhibitor with similar structure of inhibitory B7 family members. SIGLEC15 expression in HCC was explored in public databases and further examined by PCR analysis. SIGLEC15 and PD-L1 expression patterns were examined in HCC samples through immunohistochemistry. SIGLEC15 expression was knocked-down or over-expressed in HCC cell lines, and CCK8 tests were used to examine cell proliferative ability in vitro. Influences of SIGLEC15 expression on tumor growth were examined in immune deficient and immunocompetent mice respectively. Co-culture system of HCC cell lines and Jurkat cells, flow cytometry analysis of tumor infiltrated immune cells and further sequencing analyses were performed to investigate how SIGLEC15 could affect T cells in vitro and in vivo. We found SIGLEC15 was increased in HCC tumor tissues and was negatively correlated with PD-L1 in HCC samples. In vitro and in vivo models demonstrated inhibition of SIGLEC15 did not directly influence tumor proliferation. However, SIGLEC15 could promoted HCC immune evasion in immune competent mouse models. Knock-out of Siglec15 could inhibit tumor growth and reinvigorate CD8+ T cell cytotoxicity. Anti-SIGLEC15 treatment could effectively inhibit tumor growth in mouse models with or without mononuclear phagocyte deletion. Bulk and single-cell RNA sequencing data of treated mouse tumors demonstrated SIGLEC15 could interfere CD8+ T cell viability and induce cell apoptosis. In all, SIGLEC15 was negatively correlated with PD-L1 in HCC and mainly promote HCC immune evasion through inhibition of CD8+ T cell viability and cytotoxicity.© 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.