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. 2022 Oct 5;12(10):2280-2307.
doi: 10.1158/2159-8290.CD-22-0201.

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

Anne-Gaëlle Goubet  1   2   3 , Leonardo Lordello #  1   3 , Carolina Alves Costa Silva #  1   2   3   4 , Isabelle Peguillet  1   3 , Marianne Gazzano  1   3   5 , Maxime Descartes Mbogning-Fonkou  1   3 , Cassandra Thelemaque  1   3 , Cédric Lebacle  6 , Constance Thibault  7 , François Audenet  8 , Géraldine Pignot  9 , Gwenaelle Gravis  10 , Carole Helissey  11 , Luca Campedel  12 , Morgan Roupret  13 , Evanguelos Xylinas  14 , Idir Ouzaid  14 , Agathe Dubuisson  1   3 , Marine Mazzenga  1   3 , Caroline Flament  1   3 , Pierre Ly  1   3 , Virginie Marty  1   15 , Nicolas Signolle  1   15 , Allan Sauvat  1   16   17 , Thomas Sbarrato  18 , Mounia Filahi  18 , Caroline Davin  18 , Gabriel Haddad  19 , Jacques Bou Khalil  19 , Camille Bleriot  1   3 , François-Xavier Danlos  1   2   3 , Garett Dunsmore  1   2   3 , Kevin Mulder  1   2   3 , Aymeric Silvin  1   3 , Thibault Raoult  1   20 , Baptiste Archambaud  1   21 , Shaima Belhechmi  1   21 , Ivo Gomperts Boneca  22 , Nadège Cayet  23 , Maryse Moya-Nilges  23 , Adeline Mallet  23 , Romain Daillere  24 , Etienne Rouleau  25 , Camelia Radulescu  26 , Yves Allory  26 , Jacques Fieschi  18 , Mathieu Rouanne  1   2   3   27 , Florent Ginhoux  1   2   28   29 , Gwénaël Le Teuff  1   21 , Lisa Derosa  1   2   3 , Aurélien Marabelle  1   2   3   4   30 , Jeroen Van Dorp  31 , Nick Van Dijk  32 , Michiel S Van Der Heijden  31   32 , Benjamin Besse  1   2   30   33 , Fabrice Andre  1   2   30   33   34 , Miriam Merad  35   36   37   38   39 , Guido Kroemer  1   16   17   40 , Jean-Yves Scoazec  1   2   15   41 , Laurence Zitvogel #  1   2   3   4 , Yohann Loriot #  1   2   30   33   34   42
Affiliations

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

Anne-Gaëlle Goubet et al. Cancer Discov. .

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.

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