Escherichia coli –Specific CXCL13-Producing TFH Are Associated with Clinical Efficacy of Neoadjuvant PD-1 Blockade against Muscle-Invasive Bladder Cancer - Aix-Marseille Université Access content directly
Journal Articles Cancer Discovery Year : 2022

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

1 Université Paris-Saclay
2 IGR - Institut Gustave Roussy
3 ITIC - Immunologie anti-tumorale et immunothérapie des cancers
4 OncokappaB (URP_7324) - NF-kappaB, Différenciation et Cancer
5 INTIM - Immunologie intégrative des tumeurs et immunothérapie des cancers
6 CIMI - Centre d'Immunologie et des Maladies Infectieuses
7 Petites Molécules de neuroprotection, neurorégénération et remyélinisation
8 HEGP - Hôpital Européen Georges Pompidou [APHP]
9 UPCité - Université Paris Cité
10 IPC - Institut Paoli-Calmettes
11 CRCM - Centre de Recherche en Cancérologie de Marseille
12 Hôpital d'Instruction des Armées Begin
13 CHU Pitié-Salpêtrière [AP-HP]
14 AP-HP - Hôpital Bichat - Claude Bernard [Paris]
15 UMR 1015 - Immunologie des tumeurs et immunothérapie
16 AMMICa - Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse
17 CRC (UMR_S_1138 / U1138) - Centre de Recherche des Cordeliers
18 MEPHI - Microbes évolution phylogénie et infections
19 IHU Marseille - Institut Hospitalier Universitaire Méditerranée Infection
20 DITEP - Département d’Innovation Thérapeutique et essais précoces [Gustave Roussy]
21 Direction de la recherche clinique [Gustave Roussy]
22 SBE - Service de biostatistique et d'épidémiologie
23 UVSQ - Université de Versailles Saint-Quentin-en-Yvelines
24 Département de médecine oncologique [Gustave Roussy]
25 PMNCO - Prédicteurs moléculaires et nouvelles cibles en oncologie
26 Département de biologie et pathologie médicales [Gustave Roussy]
27 Oncologie gynécologique
Maxime Descartes Mbogning-Fonkou
Géraldine Pignot
Luca Campedel
Morgan Roupret
Evanguelos Xylinas
Pierre Ly
Nicolas Signolle
Allan Sauvat
Thomas Sbarrato
Mounia Filahi
Caroline Davin
Gabriel Haddad
Garett Dunsmore
Kevin Mulder
Shaima Belhechmi
Ivo Gomperts Boneca
Nadège Cayet
Maryse Moya-Nilges
Adeline Mallet
Romain Daillere
Etienne Rouleau
Jacques Fieschi
Florent Ginhoux
Gwénaël Le Teuff
Jeroen van Dorp
Nick van Dijk
Michiel van der Heijden
Miriam Merad
Guido Kroemer

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

Dates and versions

hal-03951702 , version 1 (23-01-2023)

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Cite

Anne-Gaëlle Goubet, Leonardo Lordello, Carolina Alves Costa Silva, Isabelle Peguillet, Marianne Gazzano, et al.. Escherichia coli –Specific CXCL13-Producing TFH Are Associated with Clinical Efficacy of Neoadjuvant PD-1 Blockade against Muscle-Invasive Bladder Cancer. Cancer Discovery, 2022, 12 (10), pp.2280-2307. ⟨10.1158/2159-8290.CD-22-0201⟩. ⟨hal-03951702⟩
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