Dissemin is shutting down on January 1st, 2025

Published in

American Association for Cancer Research, Cancer Discovery, 10(12), p. 2280-2307, 2022

DOI: 10.1158/2159-8290.cd-22-0201

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Escherichia coli–Specific CXCL13-Producing TFH Are Associated with Clinical Efficacy of Neoadjuvant PD-1 Blockade against Muscle-Invasive Bladder Cancer

Journal article published in 2022 by Anne-Gaëlle Goubet ORCID, Leonardo Lordello ORCID, Carolina Alves Costa Silva ORCID, Isabelle Peguillet ORCID, Marianne Gazzano ORCID, Maxime Descartes Mbogning-Fonkou ORCID, Cassandra Thelemaque ORCID, Cédric Lebacle ORCID, Constance Thibault ORCID, François Audenet ORCID, Géraldine Pignot ORCID, Gwenaelle Gravis ORCID, Carole Helissey ORCID, Luca Campedel ORCID, Morgan Roupret ORCID and other authors.
This paper was not found in any repository, but could be made available legally by the author.
This paper was not found in any repository, but could be made available legally by the author.

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Abstract

Abstract Biomarkers guiding the neoadjuvant use of immune-checkpoint blockers (ICB) are needed for patients with localized muscle-invasive bladder cancers (MIBC). Profiling tumor and blood samples, we found that follicular helper CD4+ T cells (TFH) are among the best therapeutic targets of pembrolizumab correlating with progression-free survival. TFH were associated with tumoral CD8 and PD-L1 expression at baseline and the induction of tertiary lymphoid structures after pembrolizumab. Blood central memory TFH accumulated in tumors where they produce CXCL13, a chemokine found in the plasma of responders only. IgG4+CD38+ TFH residing in bladder tissues correlated with clinical benefit. Finally, TFH and IgG directed against urothelium-invasive Escherichia coli dictated clinical responses to pembrolizumab in three independent cohorts. The links between tumor infection and success of ICB immunomodulation should be prospectively assessed at a larger scale. Significance: In patients with bladder cancer treated with neoadjuvant pembrolizumab, E. coli–specific CXCL13 producing TFH and IgG constitute biomarkers that predict clinical benefit. Beyond its role as a biomarker, such immune responses against E. coli might be harnessed for future therapeutic strategies. This article is highlighted in the In This Issue feature, p. 2221