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Scientific article
Open access
English

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

Published inJournal of Clinical Investigation, vol. 127, no. 8, p. 2916-2929
Publication date2017
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.

Keywords
  • Administration
  • Intravesical
  • Aged
  • Aged
  • 80 and over
  • BCG Vaccine
  • Disease-Free Survival
  • Female
  • Humans
  • Immune System
  • Immunotherapy
  • Interleukin-13/metabolism
  • Longitudinal Studies
  • Lymphocytes/cytology
  • Male
  • Middle Aged
  • Monocytes/cytology
  • Neoplasm Recurrence
  • Local/immunology/urine
  • Neutrophils/cytology
  • Prospective Studies
  • T-Lymphocytes/cytology
  • Urinary Bladder Neoplasms/immunology/therapy/urine
Affiliation Not a UNIGE publication
Funding
  • Swiss National Science Foundation - Ambizione PZOOP3_161459
Citation (ISO format)
CHEVALIER, Mathieu F et al. ILC2-modulated T cell-to-MDSC balance is associated with bladder cancer recurrence. In: Journal of Clinical Investigation, 2017, vol. 127, n° 8, p. 2916–2929. doi: 10.1172/JCI89717
Main files (1)
Article (Published version)
Identifiers
ISSN of the journal0021-9738
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