ILC2-modulated T cell-to-MDSC balance is associated with bladder cancer recurrence.

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Version: author
Serval ID
serval:BIB_FA350D3E0400
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
ILC2-modulated T cell-to-MDSC balance is associated with bladder cancer recurrence.
Journal
The Journal of Clinical Investigation
Author(s)
Chevalier M.F., Trabanelli S., Racle J., Salomé B., Cesson V., Gharbi D., Bohner P., Domingos-Pereira S., Dartiguenave F., Fritschi A.S., Speiser D.E., Rentsch C.A., Gfeller D., Jichlinski P., Nardelli-Haefliger D., Jandus C., Derré L.
ISSN
1558-8238 (Electronic)
ISSN-L
0021-9738
Publication state
Published
Issued date
2017
Peer-reviewed
Oui
Volume
127
Number
8
Pages
2916-2929
Language
english
Abstract
Non-muscle-invasive bladder cancer (NMIBC) is a highly recurrent tumor despite intravesical immunotherapy instillation with the bacillus Calmette-Guérin (BCG) vaccine. In a prospective longitudinal study, we took advantage of BCG instillations, which increase local immune infiltration, to characterize immune cell populations in the urine of patients with NMIBC as a surrogate for the bladder tumor microenvironment. We observed an infiltration of neutrophils, T cells, monocytic myeloid-derived suppressor cells (M-MDSCs), and group 2 innate lymphoid cells (ILC2). Notably, patients with a T cell-to-MDSC ratio of less than 1 showed dramatically lower recurrence-free survival than did patients with a ratio of greater than 1. Analysis of early and later time points indicated that this patient dichotomy existed prior to BCG treatment. ILC2 frequency was associated with detectable IL-13 in the urine and correlated with the level of recruited M-MDSCs, which highly expressed IL-13 receptor α1. In vitro, ILC2 were increased and potently expressed IL-13 in the presence of BCG or tumor cells. IL-13 induced the preferential recruitment and suppressive function of monocytes. Thus, the T cell-to-MDSC balance, associated with a skewing toward type 2 immunity, may predict bladder tumor recurrence and influence the mortality of patients with muscle-invasive cancer. Moreover, these results underline the ILC2/IL-13 axis as a targetable pathway to curtail the M-MDSC compartment and improve bladder cancer treatment.

Pubmed
Web of science
Open Access
Yes
Create date
28/06/2017 13:20
Last modification date
20/08/2019 16:25
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