title: Intralymphatic mRNA vaccine induces CD8 T-cell responses that inhibit the growth of mucosally located tumours.
abstract: The lack of appropriate mouse models is likely one of the reasons of a limited translational success rate of therapeutic vaccines against cervical cancer, as rapidly growing ectopic tumours are commonly used for preclinical studies. In this work, we demonstrate that the tumour microenvironment of TC-1 tumours differs significantly depending on the anatomical location of tumour lesions (i.e. subcutaneously, in the lungs and in the genital tract). Our data demonstrate that E7-TriMix mRNA vaccine-induced CD8(+) T lymphocytes migrate into the tumour nest and control tumour growth, although they do not express mucosa-associated markers such as CD103 or CD49a. We additionally show that despite the presence of the antigen-specific T cells in the tumour lesions, the therapeutic outcomes in the genital tract model remain limited. Here, we report that such a hostile tumour microenvironment can be reversed by cisplatin treatment, leading to a complete regression of clinically relevant tumours when combined with mRNA immunization. We thereby demonstrate the necessity of utilizing clinically relevant models for preclinical evaluation of anticancer therapies and the importance of a simultaneous combination of anticancer immune response induction with targeting of tumour environment.
authors.affiliation: Laboratory of Molecular and Cellular Therapy, Vrije Universiteit Brussel, Laarbeeklaan 103E, 1090 Brussels, Belgium.
authors.forename: Lukasz
authors.initials: L
authors.lastname: Bialkowski
authors.affiliation: Laboratory of Molecular and Cellular Therapy, Vrije Universiteit Brussel, Laarbeeklaan 103E, 1090 Brussels, Belgium.
authors.forename: Alexia
authors.initials: A
authors.lastname: van Weijnen
authors.affiliation: Laboratory of Molecular and Cellular Therapy, Vrije Universiteit Brussel, Laarbeeklaan 103E, 1090 Brussels, Belgium.
authors.forename: Kevin
authors.initials: K
authors.lastname: Van der Jeught
authors.affiliation: Laboratory of Molecular and Cellular Therapy, Vrije Universiteit Brussel, Laarbeeklaan 103E, 1090 Brussels, Belgium.
authors.forename: Dries
authors.initials: D
authors.lastname: Renmans
authors.affiliation: Laboratory of Molecular and Cellular Therapy, Vrije Universiteit Brussel, Laarbeeklaan 103E, 1090 Brussels, Belgium.
authors.forename: Lidia
authors.initials: L
authors.lastname: Daszkiewicz
authors.affiliation: Laboratory of Molecular and Cellular Therapy, Vrije Universiteit Brussel, Laarbeeklaan 103E, 1090 Brussels, Belgium.
authors.forename: Carlo
authors.initials: C
authors.lastname: Heirman
authors.affiliation: Diabetes Research Center, Vrije Universiteit Brussel, Laarbeeklaan 103E, 1090 Brussels, Belgium.
authors.forename: Geert
authors.initials: G
authors.lastname: Stangé
authors.affiliation: Laboratory of Molecular and Cellular Therapy, Vrije Universiteit Brussel, Laarbeeklaan 103E, 1090 Brussels, Belgium.
authors.forename: Karine
authors.initials: K
authors.lastname: Breckpot
authors.affiliation: Laboratory of Molecular and Cellular Therapy, Vrije Universiteit Brussel, Laarbeeklaan 103E, 1090 Brussels, Belgium.
authors.forename: Joeri L
authors.initials: JL
authors.lastname: Aerts
authors.affiliation: Laboratory of Molecular and Cellular Therapy, Vrije Universiteit Brussel, Laarbeeklaan 103E, 1090 Brussels, Belgium.
authors.forename: Kris
authors.initials: K
authors.lastname: Thielemans
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009092:Mucous Membrane / Q000473:pathology*; D012333:RNA, Messenger / Q000276:immunology*; D059016:Tumor Microenvironment; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000473:pathology; D014612:Vaccines / Q000008:administration & dosage* / Q000276:immunology
chemical_list: D019496:Cancer Vaccines; D012333:RNA, Messenger; D014612:Vaccines