Highlights
- •CXCL13 expression predicts survival for advanced-stage MIBC treated with ICI.
- •CXCL13 expression correlates with the presence of TLS in TCGA tumours.
- •Ba/Sq and stroma-rich subtypes have higher CXCL13 expression and harbour more TLS.
- •We suggest CXCL13 as a predictive biomarker for ICI response in bladder cancer.
Abstract
Introduction
Immune checkpoint inhibitors (ICIs) have proved to be an effective treatment for up
to 40% of muscle-invasive bladder cancer (MIBC), but there is still a need for better
performing biomarkers allowing to improve prediction of response to ICI. Response
to immunotherapy in soft-tissue sarcoma, melanoma and renal cell carcinoma have been
recently linked to the presence of tertiary lymphoid structures (TLS) in the tumour.
TLS are organised aggregates of T, B and dendritic cells, participating in adaptive
antitumor immune response. The chemokine CXCL13 is involved in the formation of TLS, and is reported as a reliable transcriptomic
marker of TLS.
Objectives
In this study, we sought to assess whether CXCL13 transcript expression can be a prognostic biomarker for ICI-treated MIBC patients
and also investigated whether it can serve a biomarker of TLS in MIBC.
Methods
We analysed transcriptomic data from three publicly available MIBC cohorts and evaluated
pathological slides from the TCGA-BLCA cohort for TLS presence and stage of maturation.
Results
We showed that CXCL13 was independently associated with both prolonged survival (HR = 0.8, 95% CI [0.68–0.94])
and objective response (p < 0.0001) in patients treated with ICI, at the difference of others immunological
signatures. However, it was not a predictor for non–ICI-treated MIBC, suggesting a
predictive effect of ICI efficacy. Finally, we validated that CXCL13 expression was correlated with tumour TLS in TCGA data set (p < 0.001), and can serve as a marker of TLS in bladder cancer.
Conclusion
These results support that CXCL13 expression, as a surrogate for tumour TLS, is a relevant candidate predictive biomarker
of response to ICI for patients with advanced-stage bladder cancer.
Graphical abstract
Graphical Abstract
Keywords
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Article info
Publication history
Published online: March 18, 2021
Accepted:
January 29,
2021
Received in revised form:
December 22,
2020
Received:
October 23,
2020
Identification
Copyright
© 2021 Elsevier Ltd. All rights reserved.
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- CXCL13 shapes tertiary lymphoid structures and promotes response to immunotherapy in bladder cancerEuropean Journal of CancerVol. 151
- PreviewThe CXC-chemokine ligand 13 (CXCL13) was identified 20 years ago and described as a key regulator of B cells migration to secondary lymphoid organs (Ansel et al. Nature 2000, Gunn et al. Nature 1998). The main function of CXCL13 is to control the recruitment and organization of B cells within lymphoid follicles. CXCL13 selectively binds to the chemokine receptor CXCR5 (CD185), which is normally expressed on mature B cells and a subset of CD4+ T cells called follicular helper T (Tfh) cells and follicular dendritic cells.
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