Conventional and PD-L1-expressing Regulatory T Cells are Enriched During BCG Therapy and may Limit its Efficacy.

Details

Serval ID
serval:BIB_09E73A101B01
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Conventional and PD-L1-expressing Regulatory T Cells are Enriched During BCG Therapy and may Limit its Efficacy.
Journal
European urology
Author(s)
Chevalier M.F., Schneider A.K., Cesson V., Dartiguenave F., Lucca I., Jichlinski P., Nardelli-Haefliger D., Derré L.
ISSN
1873-7560 (Electronic)
ISSN-L
0302-2838
Publication state
Published
Issued date
11/2018
Peer-reviewed
Oui
Volume
74
Number
5
Pages
540-544
Language
english
Notes
Publication types: Letter ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
The regulation of immune responses occurring during Bacillus Calmette-Guerin (BCG) therapy need to be better scrutinized in order to identify new targetable pathways for non-muscle invasive bladder cancer treatment. Immunoregulatory mechanisms have emerged as key players in various cancers. While T lymphocytes are crucial for the control of tumor growth, they often include regulatory subsets known to restrain their anti-tumor activity. In this prospective study, we assessed conventional regulatory T cells (cTregs) and PD-L1-expressing CD4 T cells (PD-L1 <sup>+</sup> Tregs) levels in blood and urine of urothelial cancer (UCa) patients undergoing BCG treatment. Local cTregs were found at higher frequencies than their counterpart in the periphery and induced by bladder tumor cells in vitro. Interestingly, while circulating PD-L1 <sup>+</sup> Tregs were hardly detectable in the blood of healthy donors and UCa patients, substantial levels were found in patients' urine. In vitro experiments suggested that BCG infection of urothelial cells could induce PD-L1 <sup>+</sup> Tregs, partially via an interferon-β-mediated mechanism. Of note, high level of Tregs in urine was associated with rapid recurrence following BCG therapy. Our findings demonstrate that T lymphocytes recruited during BCG therapy encompass a significant fraction of regulatory cells including a non-classical source of PD-L1 and reinforce treatment strategies combining BCG with PD-1/PD-L1 checkpoint inhibitors as promising approaches for non-muscle invasive bladder cancer.
We investigated the presence of particular immune cell types in the urine of bladder cancer patients undergoing Bacillus Calmette-Guerin (BCG) therapy. We identified a cell type that is strongly enriched in the urine after BCG instillation and that may favor tumor recurrence. This immune subpopulation might be targeted for bladder cancer treatment.
Keywords
Administration, Intravesical, B7-H1 Antigen/immunology, BCG Vaccine/administration & dosage, BCG Vaccine/adverse effects, CD4 Lymphocyte Count, Case-Control Studies, Cell Line, Tumor, Coculture Techniques, Humans, Prospective Studies, T-Lymphocytes, Regulatory/immunology, T-Lymphocytes, Regulatory/pathology, Time Factors, Treatment Outcome, Urinary Bladder Neoplasms/immunology, Urinary Bladder Neoplasms/pathology, Urinary Bladder Neoplasms/therapy, Urinary Bladder Neoplasms/urine, Urine/cytology, Urothelium/immunology, Urothelium/pathology, BCG therapy, Immune checkpoint, Immunoregulation, PD-L1, Tregs, Urothelial cancer
Pubmed
Web of science
Create date
31/07/2018 10:23
Last modification date
20/08/2019 12:31
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