IL-16 processing in sentinel node regulatory T cells is a factor in bladder cancer immunity.
Aged
Aged, 80 and over
Female
Flow Cytometry
Humans
Interleukin-16
/ metabolism
Male
Muscle Neoplasms
/ immunology
Neoplasm Staging
Proteomics
Sentinel Lymph Node
/ immunology
Signal Transduction
T-Lymphocyte Subsets
/ immunology
T-Lymphocytes, Regulatory
/ immunology
Tumor Escape
Urinary Bladder Neoplasms
/ immunology
Urothelium
/ pathology
IL-16
proteomics
regulatory T cells
sentinel node
urinary bladder cancer
Journal
Scandinavian journal of immunology
ISSN: 1365-3083
Titre abrégé: Scand J Immunol
Pays: England
ID NLM: 0323767
Informations de publication
Date de publication:
Dec 2020
Dec 2020
Historique:
received:
09
11
2019
revised:
18
06
2020
accepted:
27
06
2020
pubmed:
31
8
2020
medline:
15
12
2020
entrez:
31
8
2020
Statut:
ppublish
Résumé
In the effort of developing new immunotherapies, the sentinel node (SN) has proven a promising source from which to harness an effective antitumour T cell response. However, tumour immune escape, a process in which regulatory T cells (Tregs) play a central role, remains a major limiting factor. Therefore, there is a clear need to increase the knowledge of Treg function and signalling in sentinel nodes. Here, we set out to explore whether the proteome in SN-resident T cells is altered by the tumour and to identify key proteins in SN T cell signalling, focusing on Tregs. Five patients with muscle-invasive urothelial bladder cancer were prospectively included. Mass spectrometry was performed on two patients, with validation and functional studies being performed on three additional patients and four healthy donors. At cystectomy, SN, non-SN lymph nodes and peripheral blood samples were collected from the patients and T cell subsets isolated through flow cytometry before downstream experiments. Proteomic analysis indicated that growth and immune signalling pathways are upregulated in SN-resident Tregs. Furthermore, centrality analysis identified the cytokine IL-16 to be central in the SN-Treg signalling network. We show that tumour-released factors, through activating caspase-3, increase Treg IL-16 processing into bioactive forms, reinforcing Treg suppressive capacity. In conclusion, we provide evidence that Tregs exposed to secreted factors from bladder tumours show increased immune and growth signalling and altered IL-16 processing which translates to enhanced Treg suppressive function, indicating altered IL-16 signalling as a novel tumour immune escape mechanism.
Substances chimiques
Interleukin-16
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e12926Subventions
Organisme : The regional Research council (RFR) in the Uppsala-Örebro region
Organisme : Lions Cancer Research Foundation, Umeå
Organisme : Västerbotten Läns Landsting
Organisme : Cancerfonden
Organisme : Stockholms Läns Landsting
Organisme : The Cancer Research Foundation in Norrland
Informations de copyright
© 2020 The Scandinavian Foundation for Immunology.
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