title: B cells promote tumor progression in a mouse model of HPV-mediated cervical cancer.
abstract: Enhancing anti-tumor immunity and preventing tumor escape are efficient strategies to increase the efficacy of therapeutic cancer vaccines. However, the treatment of advanced tumors remains difficult, mainly due to the immunosuppressive tumor microenvironment. Regulatory T cells and myeloid-derived suppressor cells have been extensively studied, and their role in suppressing tumor immunity is now well established. In contrast, the role of B lymphocytes in tumor immunity remains unclear because B cells can promote tumor immunity or display regulatory functions to control excessive inflammation, mainly through IL-10 secretion. Here, in a mouse model of HPV-related cancer, we demonstrate that B cells accumulated in the draining lymph node of tumor-bearing mice, due to a prolonged survival, and showed a decreased expression of MHC class II and CD86 molecules and an increased expression of Ly6A/E, PD-L1 and CD39, suggesting potential immunoregulatory properties. However, B cells from tumor-bearing mice did not show an increased ability to secrete IL-10 and a deficiency in IL-10 production did not impair tumor growth. In contrast, in B cell-deficient μMT mice, tumor rejection occurred due to a strong T cell-dependent anti-tumor response. Genetic analysis based on single nucleotide polymorphisms identified genetic variants associated with tumor rejection in μMT mice, which could potentially affect reactive oxygen species production and NK cell activity. Our results demonstrate that B cells play a detrimental role in anti-tumor immunity and suggest that targeting B cells could enhance the anti-tumor response and improve the efficacy of therapeutic cancer vaccines.
authors.affiliation: Institut Pasteur, Unité de Régulation Immunitaire et Vaccinologie, Equipe Labellisée Ligue Contre le Cancer, Paris, France.|INSERM U1041, Unité de Régulation Immunitaire et Vaccinologie, Département Immunologie, Paris, France.|Université Paris Diderot, Sorbonne Paris Cité, Cellule Pasteur, Paris, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Tang
authors.affiliation: Institut Pasteur, Unité de Régulation Immunitaire et Vaccinologie, Equipe Labellisée Ligue Contre le Cancer, Paris, France.|INSERM U1041, Unité de Régulation Immunitaire et Vaccinologie, Département Immunologie, Paris, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Dadaglio
authors.affiliation: Institut Pasteur, Unité de Régulation Immunitaire et Vaccinologie, Equipe Labellisée Ligue Contre le Cancer, Paris, France.|INSERM U1041, Unité de Régulation Immunitaire et Vaccinologie, Département Immunologie, Paris, France.
authors.forename: Marine
authors.initials: M
authors.lastname: Oberkampf
authors.affiliation: Institut Pasteur, Unité Microenvironnement Et Immunité, Paris, France.
authors.forename: Selene
authors.initials: S
authors.lastname: Di Carlo
authors.affiliation: Institut Pasteur, Unité Microenvironnement Et Immunité, Paris, France.
authors.forename: Lucie
authors.initials: L
authors.lastname: Peduto
authors.affiliation: Institut Pasteur, Unité de Régulation Immunitaire et Vaccinologie, Equipe Labellisée Ligue Contre le Cancer, Paris, France.|INSERM U1041, Unité de Régulation Immunitaire et Vaccinologie, Département Immunologie, Paris, France.
authors.forename: Daphné
authors.initials: D
authors.lastname: Laubreton
authors.affiliation: Institut Pasteur, Unité de Régulation Immunitaire et Vaccinologie, Equipe Labellisée Ligue Contre le Cancer, Paris, France.|INSERM U1041, Unité de Régulation Immunitaire et Vaccinologie, Département Immunologie, Paris, France.
authors.forename: Belinda
authors.initials: B
authors.lastname: Desrues
authors.affiliation: Institut Pasteur, Unité de Régulation Immunitaire et Vaccinologie, Equipe Labellisée Ligue Contre le Cancer, Paris, France.|INSERM U1041, Unité de Régulation Immunitaire et Vaccinologie, Département Immunologie, Paris, France.
authors.forename: Cheng-Ming
authors.initials: CM
authors.lastname: Sun
authors.affiliation: Institut Pasteur, Unité de Génétique fonctionnelle de la souris, Paris, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Montagutelli
authors.affiliation: Institut Pasteur, Unité de Régulation Immunitaire et Vaccinologie, Equipe Labellisée Ligue Contre le Cancer, Paris, France.|INSERM U1041, Unité de Régulation Immunitaire et Vaccinologie, Département Immunologie, Paris, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Leclerc
mesh_terms: D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement / Q000276:immunology; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D055106:Genome-Wide Association Study; D016753:Interleukin-10 / Q000096:biosynthesis; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation; D051379:Mice; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000150:complications* / Q000821:virology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology
chemical_list: D051217:Toll-Like Receptor 9; D016753:Interleukin-10
keywords: B cells; immunosuppression; tumor microenvironment