MP01-16: IL-10 and CXCL10 urine quantification as useful biomarkers to predict BCG response in bladder cancer patients

Felix Guerrero-Ramos, Pablo Abad-Lopez, Cristian Suarez-Cabrera, Marta Rodriguez-Izquierdo, Carmen Gomez-Cañizo, Federico de la Rosa-Kehrmann, Victor Garcia-Martinez, Alejandra Bernardini, Iris Lodewijk, Guillermo Paramio, Alfredo Rodriguez-Antolin, Jesus M Paramio, Marta Dueñas

Introduction: Identifying biomarkers to predict BCG response before beginning the treatment is an unsolved need in the clinical practice for patients with high risk non-muscle invasive bladder cancer. Nowadays, there is no method to predict BCG response in our patients. In this context, protumor activity of M2 macrophages could be mediating this treatment response, so evaluation of cytokines as IL-10 and CXCL10 in urine could be an indicator of their activity on patient’s urothelium. 

The main aim of this work is to evaluate if expression levels of IL-10 and CXCL10 in urine samples obtained before treatment are able to identify BGC responders and non-responders. We also aimed to find out the correlation of these levels in urine with the presence of M2 macrophages in tumor tissue samples obtained after transurethral resection of the bladder tumor (TURBT) and before the onset of BCG instillations.

Methods: Tumor tissue samples as well as urine samples were collected from a paired sample set (n= 20) from patients before BCG treatment at our Urology Department. Response to BCG instillations was defined as no recurrence after 2 years. Informed consent was obtained from all patients. The expression levels of IL-10 and CXCL10 were measured by ELISA and RT-qPCR. The percentage of M2 polarized macrophages was calculated by immunohistochemistry staining using CD163 as M2 surface marker. We also carried out nanostring profiling with IO360 panel to characterize immune cell population in tumor tissue.

Results: We found a good correlation between the levels of IL-10 and CXCL10 measured by ELISA in urine samples and the levels determined by RT-qPCR in urine and tumor tissue. In order to define if the presence of M2 macrophages before BCG instillation correlates with the BCG response rate, we quantified CD163-positive cells in tissue samples from responders and non-responders. We found that patients with higher count of CD163+ infiltrating cells show worse response to BCG. We found that IL-10 quantification is a good predictor for BCG response.

Conclusions: The presence of M2 polarized macrophages in TURBT tissue as well as M2 markers in urine samples of bladder cancer patients appear to be predictive for BCG response. However, validation in a larger cohort is needed to confirm our data. Source of

Funding: None.