Abstract
Original language | English |
---|---|
Pages (from-to) | 2280-2307 |
Number of pages | 28 |
Journal | Cancer discovery |
Volume | 12 |
Issue number | 10 |
DOIs | |
Publication status | Published - 1 Oct 2022 |
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In: Cancer discovery, Vol. 12, No. 10, 01.10.2022, p. 2280-2307.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Escherichia coli–Specific CXCL13-Producing TFH Are Associated with Clinical Efficacy of Neoadjuvant PD-1 Blockade against Muscle- Invasive Bladder Cancer
AU - Goubet, Anne-Gaëlle
AU - Lordello, Leonardo
AU - Silva, Carolina Alves Costa
AU - Peguillet, Isabelle
AU - Gazzano, Marianne
AU - Mbogning-Fonkou, Maxime Descartes
AU - Thelemaque, Cassandra
AU - Lebacle, C. dric
AU - Thibault, Constance
AU - Audenet, François
AU - Pignot, G. raldine
AU - Gravis, Gwenaelle
AU - Helissey, Carole
AU - Campedel, Luca
AU - Roupret, Morgan
AU - Xylinas, Evanguelos
AU - Ouzaid, Idir
AU - Dubuisson, Agathe
AU - Mazzenga, Marine
AU - Flament, Caroline
AU - Ly, Pierre
AU - Marty, Virginie
AU - Signolle, Nicolas
AU - Sauvat, Allan
AU - Sbarrato, Thomas
AU - Filahi, Mounia
AU - Davin, Caroline
AU - Haddad, Gabriel
AU - Khalil, Jacques Bou
AU - Bleriot, Camille
AU - Danlos, François-Xavier
AU - Dunsmore, Garett
AU - Mulder, Kevin
AU - Silvin, Aymeric
AU - Raoult, Thibault
AU - Archambaud, Baptiste
AU - Belhechmi, Shaima
AU - Boneca, Ivo Gomperts
AU - Cayet, Nadège
AU - Moya-Nilges, Maryse
AU - Mallet, Adeline
AU - Daillere, Romain
AU - Rouleau, Etienne
AU - Radulescu, Camelia
AU - Allory, Yves
AU - Fieschi, Jacques
AU - Rouanne, Mathieu
AU - Ginhoux, Florent
AU - le Teuff, Gwénaël
AU - Derosa, Lisa
AU - Marabelle, Aurélien
AU - van Dorp, Jeroen
AU - van Dijk, Nick
AU - van der Heijden, Michiel S.
AU - Besse, Benjamin
AU - Andre, Fabrice
AU - Merad, Miriam
AU - Kroemer, Guido
AU - Scoazec, Jean-Yves
AU - Zitvogel, Laurence
AU - Loriot, Yohann
N1 - Funding Information: The trial was conducted by the French Genitourinary Group (GETUG) and funded by MSD, which provided the drug. This study was approved by the ethics committee CPP Est-III in December 2017 and the French National Agency for the Safety of Medicines and Health Products (ANSM) in November 2017, and was conducted in accordance with the protocols and Good Clinical Practice Guidelines defined by the International Conference for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use and the principles of the Declaration of Helsinki. Funding Information: We thank pathologists, nurses, and clinical research associates from Hôpital Européenn George Pompidou, Hôpital Begin, Institut Paoli-Calmettes, Hôpital Bichat, and Hôpital Pitié-Salpétrière for their participation in the PANDORE clinical trial. We are thankful to the flow and mass cytometry facility team of Gustave Roussy (Philippe Rameau and Cyril Catelain). We thank Fluidigm for their support. We are grateful for support for equipment from the French Government Programme Investissements d’Avenir France BioImag-ing (FBI; No. ANR-10-INSB-04-01) and the French Government (Agence Nationale de la Recherche) Investissement d’Avenir program, Laboratoire d’Excellence “Integrative Biology of Emerging Infectious Diseases” (ANR-10-LABX-62-IBEID). A.-G. Goubet was supported by Fondation pour la Recherche Médicale. C. Alves Costa Silva was supported by MSD Avenir. F.-X. Danlos was supported by Fondation Philantropia. M. Roupret was supported by Fondation Foch and the Association Française d’Urologie (AFU). L. Zitvogel was funded by the RHU Torino Lumière (ANR-16-RHUS-0008). L. Zitvogel and L. Derosa were supported by RHU5 “ANR-21-RHUS-0017” IMMUNOLIFE, SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE), as well as the SIGN’IT ARC foundation. L. Zitvogel was supported by European Union’s Horizon 2020 research and innovation programme under grant agreement number 825410 [project acronym: ONCOBIOME, project title: Gut OncoMicrobiome Signatures (GOMS) associated with cancer incidence, prognosis, and prediction of treatment response]. L. Zitvogel also received an ANR grant–French-German Ileobiome 19-CE15-0029-01. L. Zitvogel and G. Kroemer received a donation from the Seerave Foundation. L. Zitvogel and G. Kroemer were supported by the Ligue contre le Cancer (équipe labelisée); ANR projets blancs; Cancéropôle Ile-de-France; Fondation pour la Recherche Médicale (FRM); a donation by Elior; Institut National du Cancer (INCa); Inserm (HTE); Institut Universitaire de France; the LabEx Immuno-Oncology; and FHU CARE, Dassault, and Badinter Philantropia. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Funding Information: We thank pathologists, nurses, and clinical research associates from Hôpital Européenn George Pompidou, Hôpital Begin, Institut Paoli-Calmettes, Hôpital Bichat, and Hôpital Pitié-Salpétrière for their participation in the PANDORE clinical trial. We are thankful to the flow and mass cytometry facility team of Gustave Roussy (Philippe Rameau and Cyril Catelain). We thank Fluidigm for their support. We are grateful for support for equipment from the French Government Programme Investissements d’Avenir France BioImag-ing (FBI; No. ANR-10-INSB-04-01) and the French Government (Agence Nationale de la Recherche) Investissement d’Avenir program, Laboratoire d’Excellence “Integrative Biology of Emerging Infectious Diseases” (ANR-10-LABX-62-IBEID). A.-G. Goubet was supported by Fondation pour la Recherche Médicale. C. Alves Costa Silva was supported by MSD Avenir. F.-X. Danlos was supported by Fondation Philantropia. M. Roupret was supported by Fondation Foch and the Association Française d’Urologie (AFU). L. Zitvogel was funded by the RHU Torino Lumière (ANR-16-RHUS-0008). L. Zitvogel and L. Derosa were supported by RHU5 “ANR-21-RHUS-0017” IMMUNOLIFE, SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE), as well as the SIGN’IT ARC foundation. L. Zitvogel was supported by European Union’s Horizon 2020 research and innovation programme under grant agreement number 825410 [project acronym: ONCOBIOME, project title: Gut OncoMicrobiome Signatures (GOMS) associated with cancer incidence, prognosis, and prediction of treatment response]. L. Zitvogel also received an ANR grant–French-German Ileobiome 19-CE15-0029-01. L. Zitvogel and G. Kroemer received a donation from the Seerave Foundation. L. Zitvogel and G. Kroemer were supported by the Ligue contre le Cancer (équipe labelisée); ANR projets blancs; Cancéropôle Ile-de-France; Fondation pour la Recherche Médicale (FRM); a donation by Elior; Institut National du Cancer (INCa); Inserm (HTE); Institut Universitaire de France; the LabEx Immuno-Oncology; and FHU CARE, Dassault, and Badinter Philantropia. Publisher Copyright: © 2022 American Association for Cancer Research.
PY - 2022/10/1
Y1 - 2022/10/1
N2 - Biomarkers guiding the neoadjuvant use of immune-checkpoint blockers (ICB) are needed for patients with localized muscle-invasive bladder cancers (MIBC). Pro-filing 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 cor-related 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.
AB - Biomarkers guiding the neoadjuvant use of immune-checkpoint blockers (ICB) are needed for patients with localized muscle-invasive bladder cancers (MIBC). Pro-filing 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 cor-related 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.
UR - http://www.scopus.com/inward/record.url?scp=85139531441&partnerID=8YFLogxK
U2 - https://doi.org/10.1158/2159-8290.CD-22-0201
DO - https://doi.org/10.1158/2159-8290.CD-22-0201
M3 - Article
C2 - 35929803
SN - 2159-8274
VL - 12
SP - 2280
EP - 2307
JO - Cancer discovery
JF - Cancer discovery
IS - 10
ER -