Biomarkers guiding the neoadjuvant use of immune checkpoint inhibitors (ICBs) 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 post-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.
Cancer discovery. 2022 Aug 05 [Epub ahead of print]
Anne-Gaelle Goubet, Leonardo Lordello, Carolina Alves Costa Silva, Isabelle Peguillet, Marianne Gazzano, Maxime Descartes Mbogning-Fonkou, Cassandra Thelemaque, Cedric Lebacle, Constance Thibault, Francois Audenet, Geraldine Pignot, Gwenaelle Gravis, Carole Helissey, Luca Campedel, Morgan Roupret, Evanguelos Xylinas, Idir Ouzaid, Agathe Dubuisson, Marine Mazzenga, Caroline Flament, Pierre Ly, Virginie Marty, Nicolas Signolle, Allan Sauvat, Thomas Sbarrato, Mounia Filahi, Caroline Davin, Gabriel Haddad, Jacques Bou Khalil, Camille Bleriot, Francois-Xavier Danlos, Garett Dunsmore, Kevin Mulder, Aymeric Silvin, Thibault Raoult, Baptiste Archambaud, Shaima Belhechmi, Ivo Gomperts Boneca, Nadege Cayet, Maryse Moya-Nilges, Adeline Mallet, Romain Daillere, Etienne Rouleau, Camelia Radulescu, Yves Allory, Jacques Fieschi, Mathieu Rouanne, Florent Ginhoux, Gwenael Le Teuff, Lisa Derosa, Aurelien Marabelle, Jeroen VAN Dorp, Nick VAN Dijk, Michiel S van der Heijden, Benjamin Besse, Fabrice Andre, Miriam Merad, Guido Kroemer, Jean-Yves Scoazec, Laurence Zitvogel, Yohann Loriot
Institut Gustave Roussy, Villejuif, France., Gustave Roussy Cancer Campus (GRCC), Villejuif, France., Gustave Roussy Cancer Center, Villejuif, France., Institut Gustave Roussy, France., Bicêtre Hospital APHP University Paris Saclay, LE KREMLIN BICETRE, France., Hopital Européen Georges-Pompidou, Paris, France., Hôpital Européen Georges-Pompidou, Paris, France., Institute Paoli-Calmettes, Marseille, France., Institute Paoli-Calmettes, marseille, France., Hôpital d'instruction des Armées Bégin, Saint-Mandé, France., Breast cancer Unit, Paris, Cedex, France., Pitie Salpétrière, Paris, France., Hôpital Bichat-Claude-Bernard, France., University of Paris, Paris, France., Veracyte, Marseille, France., Aix-Marseille University, Marseille, France., Institut Hospitalo-Universitaire Méditerranée Infection, Marseille, France., Institute Curie, Paris, France., Institut Pasteur, Paris, France., Institut Pasteur, France., Hôpital Foch, Suresnes, France., Hôpital Foch, France., Singapore Immunology Network Agency for Science, Technology, and Research, Singapore, Singapore., Gustave Roussy, Univ. Paris-Sud, Université Paris-Saclay, Villejuif, France., Institut Gustave Roussy, VilleJuif, France., The Netherlands Cancer Institute, Amsterdam, Netherlands., Precision Immunology Institute, New York, NY, United States., INSERM U1138, Paris, France., Gustave Roussy Cancer Campus, Villejuif, Ile de France, France., Gustave Roussy, INSERM U981, Villejuif, France.
PubMed http://www.ncbi.nlm.nih.gov/pubmed/35929803