> Details

Goubet, Anne-Gaëlle; Lordello, Leonardo; Alves Costa Silva, Carolina; Peguillet, Isabelle; Gazzano, Marianne; Mbogning-Fonkou, Maxime Descartes; Thelemaque, Cassandra; Lebacle, Cédric; Thibault, Constance; Audenet, François; Pignot, Géraldine; Gravis, Gwenaelle; Helissey, Carole; Campedel, Luca; Roupret, Morgan; Xylinas, Evanguelos; Ouzaid, Idir; Dubuisson, Agathe; Mazzenga, Marine; Flament, Caroline; Ly, Pierre; Marty, Virginie; Signolle, Nicolas; Sauvat, Allan; [...]

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

Reference
management

Bookmarks

Remove from
bookmarks

Share this on Whatsapp

Close

Bookmarks



You can manage bookmarks using lists, please log in to your user account for this.
  • Media type: E-Article
  • Title: Escherichia coli–Specific CXCL13-Producing TFH Are Associated with Clinical Efficacy of Neoadjuvant PD-1 Blockade against Muscle-Invasive Bladder Cancer
  • Contributor: Goubet, Anne-Gaëlle; Lordello, Leonardo; Alves Costa Silva, Carolina; Peguillet, Isabelle; Gazzano, Marianne; Mbogning-Fonkou, Maxime Descartes; Thelemaque, Cassandra; Lebacle, Cédric; Thibault, Constance; Audenet, François; Pignot, Géraldine; Gravis, Gwenaelle; Helissey, Carole; Campedel, Luca; Roupret, Morgan; Xylinas, Evanguelos; Ouzaid, Idir; Dubuisson, Agathe; Mazzenga, Marine; Flament, Caroline; Ly, Pierre; Marty, Virginie; Signolle, Nicolas; Sauvat, Allan; [...]
  • Published: American Association for Cancer Research (AACR), 2022
  • Published in: Cancer Discovery, 12 (2022) 10, Seite 2280-2307
  • Language: English
  • DOI: 10.1158/2159-8290.cd-22-0201
  • ISSN: 2159-8274; 2159-8290
  • Origination:
  • Footnote:
  • Description: 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
  • Access State: Open Access