Serum CCL27 predicts the response to Bacillus Calmette-Guerin immunotherapy in non-muscle-invasive bladder cancer
Serum CCL27 predicts the response to Bacillus Calmette-Guerin immunotherapy in non-muscle-invasive bladder cancer
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血清 CCL27 预测非肌层浸润性膀胱癌卡介苗免疫治疗的反应
DOI：
10.1080/2162402x.2020.1776060
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发表时间：
2020
期刊：
影响因子：
7.2
通讯作者：
Lin T
中科院分区：
文献类型：
--
作者：
Zhong W;Wang B;Yu H;Lin J;Xia K;Hou W;Yang M;Chen J;Yang M;Wang X;Huang J;Lin T
摘要预测卡介苗（BCG）的疗效有助于鉴别非肌层浸润性膀胱癌（NMIBC）患者，这些患者可能更适合采用替代疗法。几种细胞因子谱呈现出有希望的结果，但它们难以在临床实践中使用。在这项前瞻性的纵向研究中，我们试图确定可靠的血清细胞因子/趋化因子，以预测使用BCG诱导治疗前和期间收集的样本对BCG的反应。我们使用Bio-plex多重测定来鉴定发现组（n = 13）中潜在的BCG失败相关的血清细胞因子/趋化因子。筛选后，我们将CCL 27确定为预测BCG反应的首选候选生物标志物（P = .003）。在验证集中，我们发现基线CCL 27的AUC为0.730（95% CI 0.515-0.945，P = 0.040），沿着具有67%的灵敏度和78%的特异性。从基线到最后一个时间点的变化也可以区分BCG应答者和无应答者（AUC：0.726，95% CI 0.474-0.979，P = 0.044）。此外，基于基线和CCL 27变化的血清CCL 27组合评分（CSCCL 27）可进一步提高预测准确性，AUC为0.897（95%CI 0.790-1.000，P < .001）。进一步分析CCL 27与局部/全身免疫学参数的相关性。血清CCL 27水平与肿瘤微环境中的调节性T细胞（TCLs）密切相关（P = .002），表明CCL 27可能促进TCLs募集到肿瘤微环境中。我们的研究结果表明，血清CCL 27可能是一个实用和可靠的标志物，用于预测NMIBC对BCG的反应。
ABSTRACT The prediction of the response to Bacillus Calmette-Guerin (BCG) can help identify non-muscle-invasive bladder cancer (NMIBC) patients that may be better served with alternative therapy. Several cytokine profiles present promising results, but they are difficult to use in clinical practice. In this prospective, longitudinal study, we tried to identify reliable serum cytokines/chemokines to predict the response to BCG using samples collected before and during BCG induction therapy. We used the Bio-plex multiplex assays to identify potential BCG failure-related serum cytokines/chemokines in the discovery set (n = 13). After screening, we identified CCL27 as the top candidate biomarker for predicting the response to BCG (P = .003). In the validation set, we found that the AUC of the baseline CCL27 was 0.730 (95% CI 0.515–0.945, P = .040) along with 67% sensitivity, 78% specificity. The changes from baseline to last timepoint can also distinguish BCG responders from non-responders (AUC: 0.726, 95% CI 0.474–0.979, P = .044). Moreover, the combination score of serum CCL27 (CSCCL27), based on the baseline and changes of CCL27, could further improve the predictive accuracy with an AUC of 0.897 (95% CI 0.790–1.000, P < .001). The correlations between CCL27 and local/systemic immunologic parameters were further analyzed. The level of serum CCL27 was strongly correlated with regulatory T cells (Tregs) in the tumor microenvironment (P = .002), indicating that CCL27 may promote the recruitment of Tregs into the tumor microenvironment. Our results show that serum CCL27 may represent a practical and reliable marker for the prediction of the response to BCG in NMIBC.