Siglec-6 as a New Potential Immune Checkpoint for Bladder Cancer Patients
Siglec-6 as a New Potential Immune Checkpoint for Bladder Cancer Patients
复制标题
DOI：
10.1016/j.euf.2021.06.001
复制
发表时间：
2022-05-01
影响因子：
5.4
通讯作者：
Derre, Laurent
中科院分区：
文献类型：
--
作者：
Benmerzoug, Sulayman;Chevalier, Mathieu F.;Derre, Laurent
在调节免疫的抑制性受体家族中，唾液酸结合的含有免疫球蛋白结构域的凝集素（Siglecs）最近出现为识别肿瘤细胞表面上的唾液酸化配体的免疫调节受体。然而，它们在膀胱癌（BCa）的免疫调节中的作用仍然未知。在这里，我们确定了膀胱非肿瘤和肿瘤细胞系上八种Siglec配体（SL）的存在。S2 L、S3 L和S6 L不表达，少数膀胱肿瘤细胞系表达S5 L和S14 L。相反，S7 L和S10 L在所有膀胱肿瘤细胞系上上调。我们发现S9 L在非肿瘤细胞系中的表达存在差异，而在膀胱肿瘤细胞系中高度表达。值得注意的是，S5 L、S6 L和S14 L的表达在卡介苗（BCG）感染后增加。此外，我们分析了Siglecs在来自健康供体和BCa患者的T细胞上的表达。循环T细胞仅表达Siglec-6，其在非肌肉侵袭性BCa患者中上调。此外，BCG治疗诱导尿CD 8 + T细胞过度表达Siglec-6。体外功能测定表明，Siglecs可以降低效应CD 8 + T细胞的细胞毒性功能。最后，来自两个BCa数据集（癌症基因组图谱和UROMOL队列）的分析显示，Siglec-6与肿瘤进展和不良生存期相关。我们的研究结果表明，Siglec-6可能是BCa治疗的新靶点。患者总结：我们研究了膀胱癌患者中免疫调节受体家族Siglecs的表达。我们观察到Siglec-6在非肌层浸润性膀胱癌患者的循环和尿T细胞上的表达增加。我们还表明，Siglec-6与膀胱癌患者的较低生存率相关，并可能导致膀胱癌复发。(c)2021作者（S）由Elsevier B. V.代表欧洲泌尿外科协会发布。这是一个在CC BY-NC-ND许可证下的开放获取文章（http：//creativecommons.org/licenses/by-nc-nd/4.0/）。
Among the growing family of inhibitory receptors regulating immunity, sialic acid-binding immunoglobulin domain-containing lectins (Siglecs) have recently emerged as immunoregulatory receptors recognizing sialylated ligands on tumor cell surface. However, their role in the immunoregulation of bladder cancer (BCa) remains unknown. Here, we determined the presence of eight Siglec ligands (SLs) on bladder nontumor and tumor cell lines. S2L, S3L, and S6L were not expressed, and few bladder tumor cell lines expressed S5L and S14L. In contrast, S7L and S10L were upregulated on all bladder tumor cell lines. We found a discrepency in S9L expression by nontumor cell lines, which is however highly expressed by bladder tumor cell lines. Notably, expression of S5L, S6L, and S14L was increased upon bacillus Calmette-Guerin (BCG) infection. Furthermore, we analyzed the expression of Siglecs onTcells from healthy donors and BCa patients. Circulating Tcells only expressed Siglec-6, which is upregulated in non-muscle-invasive BCa patients. In addition, BCG therapy induced the overexpression of Siglec-6 by urinary CD8+ T cells. In vitro functional assays suggested that Siglecs may decrease cytotoxic functions of effector CD8+ T cells. Finally, analyses from two BCa datasets (The Cancer Genome Atlas and UROMOL cohorts) showed that Siglec-6 is associated with tumor progression and poor survival. Our findings indicate that Siglec-6 might be a new target for BCa treatments. Patient summary: We investigated the expression of Siglecs, a family of immunoregulatory receptors, in bladder cancer patients. We observed that the expression of Siglec-6 is increased on circulating and urinary T cells of non-muscle-invasive bladder cancer patients. We also showed that Siglec-6 is associated with lower survival in bladder cancer patients and might contribute to bladder cancer recurrence.(c) 2021 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).