Ashiru Omodele, Esteso Gloria, García-Cuesta Eva M, Castellano Eva, Samba Celia, Escudero-López Eva, López-Cobo Sheila, Álvarez-Maestro Mario, Linares Ana, Ho Mei M, Leibar Asier, Martínez-Piñeiro Luis, Valés-Gómez Mar
Division of Bacteriology, Medicines and Healthcare products Regulatory Agency-National Institute for Biological Standards and Control (MHRA-NIBSC), Blanche Lane, South Mimms, Potters Bar, Hertfordshire EN6 3QG, UK.
Department of Immunology and Oncology, National Centre for Biotechnology, Spanish National Research Council, 28049 Madrid, Spain.
Cancers (Basel). 2019 Jul 4;11(7):940. doi: 10.3390/cancers11070940.
Intra-vesical instillation of (BCG), an attenuated strain of , is an effective therapy for high-grade non-muscle invasive bladder cancer (NMIBC), which provokes a local immune response resulting in 70% of patients free of relapse after three years. Because non-responder patients usually have a bad prognosis, the early identification of treatment failure is crucial. We hypothesized that, if an effective immune response was taking place in the bladder, soluble factors would be released to the urine many days after BCG instillations. An extensive panel of cytokines and chemokines released into the urine seven days after every BCG instillation was screened in a cohort of NMIBC patients over three years. The determinations of the urinary concentrations of cytokines, chemokines, and creatinine showed that increasing concentrations of C-X-C motif chemokine 10 (CXCL10) also known as interferon-inducible protein 10 (IP10) could be detected during the six-week induction cycle of BCG-treated patients released into the urine by CD14 cells. In vitro, CXCL10 facilitated the recruitment of effector immune cells after the BCG-mediated upregulation of CXCR3 in both T- and natural killer (NK)-cells. The high concentrations of chemokine detected one week after the encounter with mycobacteria suggest that the CXCL10 axis might be related to the intensity of the immune anti-tumor response.
卡介苗（BCG）是一种减毒的结核分枝杆菌菌株，膀胱内灌注卡介苗是治疗高级别非肌层浸润性膀胱癌（NMIBC）的有效方法，它能引发局部免疫反应，使70%的患者在三年后无复发。由于无反应患者通常预后不良，因此早期识别治疗失败至关重要。我们推测，如果膀胱内发生有效的免疫反应，卡介苗灌注后数天可溶性因子会释放到尿液中。在三年多的时间里，对一组NMIBC患者每次卡介苗灌注后七天释放到尿液中的大量细胞因子和趋化因子进行了筛选。细胞因子、趋化因子和肌酐的尿液浓度测定表明，在卡介苗治疗患者的六周诱导周期内，可检测到尿中C-X-C基序趋化因子10（CXCL10，也称为干扰素诱导蛋白10，即IP10）的浓度不断升高，该趋化因子由CD14细胞释放到尿液中。在体外，卡介苗介导T细胞和自然杀伤（NK）细胞表面CXCR3上调后，CXCL10促进效应免疫细胞的募集。与分枝杆菌接触一周后检测到的高浓度趋化因子表明，CXCL10轴可能与免疫抗肿瘤反应的强度有关。
