Journal Article

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

Chevalier, Mathieu F., Cesson, Valérie, Jandus, Camilla, Salomé, Bérengère, Domingos-Pereira, Sonia, Gfeller, David, Derré, Laurent, Fritschi, Anne-Sophie, Racle, Julien, Dartiguenave, Florence, Nardelli-Haefliger, Denise, Rentsch, Cyrill A., Speiser, Daniel E., Trabanelli, Sara, Gharbi, Dalila, Bohner, Perrine, Jichlinski, Patrice

2017

Overview

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.

• Publisher: American Society for Clinical Investigation
• Subject: Administration, Intravesical / Aged / Aged, 80 and over / Analysis / Antigens / Bacillus Calmette-Guerin vaccine / BCG / BCG Vaccine / Biomedical research / Bladder cancer / Cancer / Cellular signal transduction / Disease-Free Survival / Female / Gene expression / Genotype & phenotype / Humans / Immune System / Immunotherapy / Interleukin 13 / Interleukin-13 - metabolism / Invasiveness / Leprosy / Leukocytes (neutrophilic) / Longitudinal Studies / Lymphocytes / Lymphocytes - cytology / Lymphocytes T / Lymphoid cells / Male / Metastases / Middle Aged / Monocytes / Monocytes - cytology / Neoplasm Recurrence, Local - immunology / Neoplasm Recurrence, Local - urine / Neutrophils / Neutrophils - cytology / Patients / Prospective Studies / Recurrence (Disease) / Rodents / Suppressor cells / Survival analysis / T cells / T-Lymphocytes - cytology / Tumor cells / Urinary bladder / Urinary Bladder Neoplasms - immunology / Urinary Bladder Neoplasms - therapy / Urinary Bladder Neoplasms - urine / Urine