Siglec-6 as a New Potential Immune Checkpoint for Bladder Cancer Patients.
Details
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State: Public
Version: author
License: CC BY-NC-ND 4.0
UNIL restricted access
State: Public
Version: author
License: CC BY-NC-ND 4.0
Serval ID
serval:BIB_5DF4F82CD6A7
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Siglec-6 as a New Potential Immune Checkpoint for Bladder Cancer Patients.
Journal
European urology focus
ISSN
2405-4569 (Electronic)
ISSN-L
2405-4569
Publication state
Published
Issued date
05/2022
Peer-reviewed
Oui
Volume
8
Number
3
Pages
748-751
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Abstract
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-Guérin (BCG) infection. Furthermore, we analyzed the expression of Siglecs on T cells from healthy donors and BCa patients. Circulating T cells 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 <sup>+</sup> T cells. In vitro functional assays suggested that Siglecs may decrease cytotoxic functions of effector CD8 <sup>+</sup> 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.
Keywords
Antigens, CD/metabolism, Antigens, Differentiation, Myelomonocytic/metabolism, BCG Vaccine, CD8-Positive T-Lymphocytes, Humans, Lectins/metabolism, Neoplasm Recurrence, Local, Sialic Acid Binding Immunoglobulin-like Lectins/genetics, Sialic Acid Binding Immunoglobulin-like Lectins/metabolism, Urinary Bladder Neoplasms/genetics, BCG therapy, Immune checkpoint, Immunoregulation, Siglecs, Urothelial cancer
Pubmed
Web of science
Open Access
Yes
Create date
29/06/2021 10:13
Last modification date
26/07/2024 9:59