Serum CCL27 predicts the response to Bacillus Calmette-Guerin immunotherapy in non-muscle-invasive bladder cancer

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 (CS CCL27), 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.

Longitudinal urinary biomarkers of immunological activation in covid-19 patients without clinically apparent kidney disease versus acute and chronic failure

“…This is the first manuscript demonstrating targeted immunological profiles in the urine of patients with acute COVID-19 infection. It is also one of few studies demonstrating the utilization of urine as the source of immunological information 11 , 14 , 16 , 19 . The major value of the presented research is a demonstration that several immunological markers correlated with activation of the immune system, the severity of the disease, and clinical outcomes while using urine as the source material.…”

Tumor-Induced Inflammatory Cytokines and the Emerging Diagnostic Devices for Cancer Detection and Prognosis

“…Moreover, the levels of circulating cytokines, IL-1α, IL-2, and IFN-α2 are useful to monitor severe, potentially life-threatening immune-related toxicity in response to the use of checkpoint inhibitors ( 96 ). Circulating CCL-27 has also been proposed to identify patients with muscle-invasive bladder cancer that will respond to Bacillus Calmette-Guerin (BCG) treatment ( 97 ).…”

Potential Role of CXCL13/CXCR5 Signaling in Immune Checkpoint Inhibitor Treatment in Cancer

“…Variations in chemokine expression levels can result in a wide range of functions with consequential effects on the treatment response to immune checkpoint inhibitors (ICIs) among patients with cancer. Elevated or reduced expression levels of different chemokines or chemokine receptors have been associated with diverse responses to immunotherapy across multiple cancer types [ 25 , 26 , 27 ]. Chemokine activation and the downstream function of signaling effectors influence almost all of the processes involved in the immunotherapy treatment response in cancer.…”