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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.
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; Sbarrato, Thomas; Filahi, Mounia; Davin, Caroline; Haddad, Gabriel; Bou Khalil, Jacques; Bleriot, Camille; Danlos, François-Xavier; Dunsmore, Garett; Mulder, Kevin; Silvin, Aymeric; Raoult, Thibault; Archambaud, Baptiste; Belhechmi, Shaima; Gomperts Boneca, Ivo; Cayet, Nadège; Moya-Nilges, Maryse; Mallet, Adeline; Daillere, Romain; Rouleau, Etienne; Radulescu, Camelia; Allory, Yves; Fieschi, Jacques; Rouanne, Mathieu; Ginhoux, Florent; Le Teuff, Gwénaël; Derosa, Lisa.
Afiliación
  • Goubet AG; Gustave Roussy, Villejuif, France.
  • Lordello L; Faculté de Médecine, Université Paris-Saclay, Kremlin-Bicêtre, France.
  • Alves Costa Silva C; Institut National de la Santé Et de la Recherche Médicale (INSERM) U1015, Equipe Labellisée-Ligue Nationale contre le Cancer, Villejuif, France.
  • Peguillet I; Gustave Roussy, Villejuif, France.
  • Gazzano M; Institut National de la Santé Et de la Recherche Médicale (INSERM) U1015, Equipe Labellisée-Ligue Nationale contre le Cancer, Villejuif, France.
  • Mbogning-Fonkou MD; Gustave Roussy, Villejuif, France.
  • Thelemaque C; Faculté de Médecine, Université Paris-Saclay, Kremlin-Bicêtre, France.
  • Lebacle C; Institut National de la Santé Et de la Recherche Médicale (INSERM) U1015, Equipe Labellisée-Ligue Nationale contre le Cancer, Villejuif, France.
  • Thibault C; Center of Clinical Investigations for In Situ Biotherapies of Cancer (BIOTHERIS), INSERM CIC1428, Villejuif, France.
  • Audenet F; Gustave Roussy, Villejuif, France.
  • Pignot G; Institut National de la Santé Et de la Recherche Médicale (INSERM) U1015, Equipe Labellisée-Ligue Nationale contre le Cancer, Villejuif, France.
  • Gravis G; Gustave Roussy, Villejuif, France.
  • Helissey C; Institut National de la Santé Et de la Recherche Médicale (INSERM) U1015, Equipe Labellisée-Ligue Nationale contre le Cancer, Villejuif, France.
  • Campedel L; Sorbonne Université, Inserm, Centre d'immunologie et des maladies infectieuses (CIMI-Paris), Département d'immunologie, Assistance Publique Hôpitaux de Paris (AP-HP), Hôpital Pitié-Salpêtrière, Paris, France.
  • Roupret M; Gustave Roussy, Villejuif, France.
  • Xylinas E; Institut National de la Santé Et de la Recherche Médicale (INSERM) U1015, Equipe Labellisée-Ligue Nationale contre le Cancer, Villejuif, France.
  • Ouzaid I; Gustave Roussy, Villejuif, France.
  • Dubuisson A; Institut National de la Santé Et de la Recherche Médicale (INSERM) U1015, Equipe Labellisée-Ligue Nationale contre le Cancer, Villejuif, France.
  • Mazzenga M; Urology Department, University Hospital of Bicêtre-Paris Sud-Saclay University, Le Kremlin Bicêtre, Paris, France.
  • Flament C; Oncology Department, Hôpital Européen Georges Pompidou, AP-HP, University of Paris, Paris, France.
  • Ly P; Department of Urology, Hôpital Européen Georges Pompidou, AP-HP Centre, Université de Paris, Paris, France.
  • Marty V; Department of Surgical Oncology 2, Institut Paoli-Calmettes Cancer Center, Marseille, France.
  • Signolle N; Department of Medical Oncology, Institut Paoli-Calmettes, Aix-Marseille University, CRCM, Marseille, France.
  • Sauvat A; Military Hospital Begin, Saint-Mandé, France.
  • Sbarrato T; Sorbonne Université, AP-HP, hôpital de La Pitié-Salpêtrière, Institut universitaire de cancérologie, département d'oncologie médicale, CLIP2 Galilée, Paris, France.
  • Filahi M; GRC 5 Predictive Onco-Uro, Sorbonne University, Department of Urology, AP-HP, Pitie-Salpetriere Hospital, Paris, France.
  • Davin C; Department of Urology, Bichat-Claude Bernard Hospital, Paris University, Paris France.
  • Haddad G; Department of Urology, Bichat-Claude Bernard Hospital, Paris University, Paris France.
  • Bou Khalil J; Gustave Roussy, Villejuif, France.
  • Bleriot C; Institut National de la Santé Et de la Recherche Médicale (INSERM) U1015, Equipe Labellisée-Ligue Nationale contre le Cancer, Villejuif, France.
  • Danlos FX; Gustave Roussy, Villejuif, France.
  • Dunsmore G; Institut National de la Santé Et de la Recherche Médicale (INSERM) U1015, Equipe Labellisée-Ligue Nationale contre le Cancer, Villejuif, France.
  • Mulder K; Gustave Roussy, Villejuif, France.
  • Silvin A; Institut National de la Santé Et de la Recherche Médicale (INSERM) U1015, Equipe Labellisée-Ligue Nationale contre le Cancer, Villejuif, France.
  • Raoult T; Gustave Roussy, Villejuif, France.
  • Archambaud B; Institut National de la Santé Et de la Recherche Médicale (INSERM) U1015, Equipe Labellisée-Ligue Nationale contre le Cancer, Villejuif, France.
  • Belhechmi S; Gustave Roussy, Villejuif, France.
  • Gomperts Boneca I; Experimental and Translational Pathology Platform (PETRA), AMMICa, INSERM US23/UAR3655, Gustave Roussy, Villejuif, France.
  • Cayet N; Gustave Roussy, Villejuif, France.
  • Moya-Nilges M; Experimental and Translational Pathology Platform (PETRA), AMMICa, INSERM US23/UAR3655, Gustave Roussy, Villejuif, France.
  • Mallet A; Gustave Roussy, Villejuif, France.
  • Daillere R; Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, Institut National de la Santé et de la Recherche Médicale U1138, Université de Paris, Sorbonne Université, Paris, France.
  • Rouleau E; Metabolomics and Cell Biology Platforms, Gustave Roussy, Villejuif, France.
  • Radulescu C; Veracyte, Marseille, France.
  • Allory Y; Veracyte, Marseille, France.
  • Fieschi J; Veracyte, Marseille, France.
  • Rouanne M; Aix-Marseille University, IRD, APHM, MEPHI, Institut Hospitalo-Universitaire Méditerranée Infection, Marseille, France.
  • Ginhoux F; Aix-Marseille University, IRD, APHM, MEPHI, Institut Hospitalo-Universitaire Méditerranée Infection, Marseille, France.
  • Le Teuff G; Gustave Roussy, Villejuif, France.
  • Derosa L; Institut National de la Santé Et de la Recherche Médicale (INSERM) U1015, Equipe Labellisée-Ligue Nationale contre le Cancer, Villejuif, France.
Cancer Discov ; 12(10): 2280-2307, 2022 10 05.
Article en En | MEDLINE | ID: mdl-35929803
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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Vejiga Urinaria Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Cancer Discov Año: 2022 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Vejiga Urinaria Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Cancer Discov Año: 2022 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Estados Unidos