<i>Escherichia coli</i>–Specific CXCL13-Producing TFH Are Associated with Clinical Efficacy of Neoadjuvant PD-1 Blockade against Muscle-Invasive Bladder Cancer-Reference-Cited by-同舟云学术

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

Published:2022-08-05 Issue:10 Volume:12 Page:2280-2307
ISSN:2159-8274
Container-title:Cancer Discovery
language:en
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Author:

Goubet Anne-Gaëlle¹²³^ORCID,Lordello Leonardo¹³^ORCID,Alves Costa Silva Carolina¹²³⁴^ORCID,Peguillet Isabelle¹³^ORCID,Gazzano Marianne¹³⁵^ORCID,Mbogning-Fonkou Maxime Descartes¹³^ORCID,Thelemaque Cassandra¹³^ORCID,Lebacle Cédric⁶^ORCID,Thibault Constance⁷^ORCID,Audenet François⁸^ORCID,Pignot Géraldine⁹^ORCID,Gravis Gwenaelle¹⁰^ORCID,Helissey Carole¹¹^ORCID,Campedel Luca¹²^ORCID,Roupret Morgan¹³^ORCID,Xylinas Evanguelos¹⁴^ORCID,Ouzaid Idir¹⁴^ORCID,Dubuisson Agathe¹³^ORCID,Mazzenga Marine¹³^ORCID,Flament Caroline¹³^ORCID,Ly Pierre¹³^ORCID,Marty Virginie¹¹⁵^ORCID,Signolle Nicolas¹¹⁵^ORCID,Sauvat Allan¹¹⁶¹⁷^ORCID,Sbarrato Thomas¹⁸^ORCID,Filahi Mounia¹⁸^ORCID,Davin Caroline¹⁸^ORCID,Haddad Gabriel¹⁹^ORCID,Bou Khalil Jacques¹⁹^ORCID,Bleriot Camille¹³^ORCID,Danlos François-Xavier¹²³^ORCID,Dunsmore Garett¹²³^ORCID,Mulder Kevin¹²³^ORCID,Silvin Aymeric¹³^ORCID,Raoult Thibault¹²⁰^ORCID,Archambaud Baptiste¹²¹^ORCID,Belhechmi Shaima¹²¹^ORCID,Gomperts Boneca Ivo²²^ORCID,Cayet Nadège²³^ORCID,Moya-Nilges Maryse²³^ORCID,Mallet Adeline²³^ORCID,Daillere Romain²⁴^ORCID,Rouleau Etienne²⁵^ORCID,Radulescu Camelia²⁶^ORCID,Allory Yves²⁶^ORCID,Fieschi Jacques¹⁸^ORCID,Rouanne Mathieu¹²³²⁷^ORCID,Ginhoux Florent¹²²⁸²⁹^ORCID,Le Teuff Gwénaël¹²¹^ORCID,Derosa Lisa¹²³^ORCID,Marabelle Aurélien¹²³⁴³⁰^ORCID,Van Dorp Jeroen³¹^ORCID,Van Dijk Nick³²^ORCID,Van Der Heijden Michiel S.³¹³²^ORCID,Besse Benjamin¹²³⁰³³^ORCID,Andre Fabrice¹²³⁰³³³⁴^ORCID,Merad Miriam³⁵³⁶³⁷³⁸³⁹^ORCID,Kroemer Guido¹¹⁶¹⁷⁴⁰^ORCID,Scoazec Jean-Yves¹²¹⁵⁴¹^ORCID,Zitvogel Laurence¹²³⁴^ORCID,Loriot Yohann¹²³⁰³³³⁴⁴²^ORCID

Affiliation:

1. 1Gustave Roussy, Villejuif, France.

2. 2Faculté de Médecine, Université Paris-Saclay, Kremlin-Bicêtre, France.

3. 3Institut National de la Santé Et de la Recherche Médicale (INSERM) U1015, Equipe Labellisée—Ligue Nationale contre le Cancer, Villejuif, France.

4. 4Center of Clinical Investigations for In Situ Biotherapies of Cancer (BIOTHERIS), INSERM CIC1428, Villejuif, France.

5. 5Sorbonne 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.

6. 6Urology Department, University Hospital of Bicêtre-Paris Sud-Saclay University, Le Kremlin Bicêtre, Paris, France.

7. 7Oncology Department, Hôpital Européen Georges Pompidou, AP-HP, University of Paris, Paris, France.

8. 8Department of Urology, Hôpital Européen Georges Pompidou, AP-HP Centre, Université de Paris, Paris, France.

9. 9Department of Surgical Oncology 2, Institut Paoli-Calmettes Cancer Center, Marseille, France.

10. 10Department of Medical Oncology, Institut Paoli-Calmettes, Aix-Marseille University, CRCM, Marseille, France.

11. 11Military Hospital Begin, Saint-Mandé, France.

12. 12Sorbonne Université, AP-HP, hôpital de La Pitié-Salpêtrière, Institut universitaire de cancérologie, département d'oncologie médicale, CLIP2 Galilée, Paris, France.

13. 13GRC 5 Predictive Onco-Uro, Sorbonne University, Department of Urology, AP-HP, Pitie-Salpetriere Hospital, Paris, France.

14. 14Department of Urology, Bichat-Claude Bernard Hospital, Paris University, Paris France.

15. 15Experimental and Translational Pathology Platform (PETRA), AMMICa, INSERM US23/UAR3655, Gustave Roussy, Villejuif, France.

16. 16Equipe 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.

17. 17Metabolomics and Cell Biology Platforms, Gustave Roussy, Villejuif, France.

18. 18Veracyte, Marseille, France.

19. 19Aix-Marseille University, IRD, APHM, MEPHI, Institut Hospitalo-Universitaire Méditerranée Infection, Marseille, France.

20. 20Service de Promotion des Etudes Cliniques (SPEC), Gustave Roussy, Université Paris-Saclay, Villejuif, France.

21. 21Service de Biostatistiques et d'Epidemiologie, Gustave Roussy, Villejuif, France.

22. 22Institut Pasteur, Université de Paris, CNRS UMR2001, INSERM U1306, Unité de Biologie et Génétique de la paroi bactérienne, Paris, France.

23. 23Core Facility Ultrastructural BioImaging Core Facility, Institut Pasteur, Paris France.

24. 24EverImmune, Gustave Roussy, Villejuif, France.

25. 25Department of Medical Biology and Pathology, Cancer Genetics Laboratory, Gustave Roussy, Villejuif, France.

26. 26Department of Pathology, Hôpital Foch, UVSQ-Université Paris-Saclay, Suresnes, France.

27. 27Department of Urology, Hôpital Foch, UVSQ-Université Paris-Saclay, Suresnes, France.

28. 28Singapore Immunology Network (SIgN), A*STAR, Singapore, Singapore.

29. 29Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

30. 30Cancer Medicine Department, Gustave Roussy, Villejuif, France.

31. 31Department of Molecular Carcinogenesis, Netherlands Cancer Institute, Amsterdam, the Netherlands.

32. 32Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands.

33. 33INSERM U981, Biomarqueurs Prédictifs et Nouvelles Stratégies Thérapeutiques en Oncologie, Villejuif, France.

34. 34PRISM precision cancer center, Gustave Roussy, Villejuif, France.

35. 35The Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York.

36. 36Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, New York.

37. 37The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York.

38. 38Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.

39. 39Institute for Thoracic Oncology, Icahn School of Medicine at Mount Sinai, New York, New York.

40. 40Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France.

41. 41Department of Medical Biology and Pathology, Gustave Roussy, Villejuif, France.

42. 42Early Drug Development Department (DITEP), Gustave Roussy, Villejuif, France.

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

Funder

Fondation pour la Recherche Médicale

RHU5

RHU Torino Lumiere

ANR

EU-H2020

Publisher

American Association for Cancer Research (AACR)

Subject

Oncology

Link

https://aacrjournals.org/cancerdiscovery/article-pdf/doi/10.1158/2159-8290.CD-22-0201/3185941/cd-22-0201.pdf