Intravesical Ty21a Vaccine Promotes Dendritic Cells and T Cell-Mediated Tumor Regression in the MB49 Bladder Cancer Model.

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Serval ID
serval:BIB_2BADE2231C76
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Intravesical Ty21a Vaccine Promotes Dendritic Cells and T Cell-Mediated Tumor Regression in the MB49 Bladder Cancer Model.
Journal
Cancer immunology research
Author(s)
Domingos-Pereira S., Sathiyanadan K., La Rosa S., Polák L., Chevalier M.F., Martel P., Hojeij R., Derré L., Haefliger J.A., Jichlinski P., Nardelli-Haefliger D.
ISSN
2326-6074 (Electronic)
ISSN-L
2326-6066
Publication state
Published
Issued date
04/2019
Peer-reviewed
Oui
Volume
7
Number
4
Pages
621-629
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Preclinical data show that intravesical instillation of Ty21a/Vivotif, a commercial vaccine against typhoid fever, is an effective alternative option to standard Bacillus Calmette-Guérin (BCG) immunotherapy for non-muscle-invasive bladder cancer (NMIBC). Here, we characterized the inflammatory effects of Ty21a on the bladder and investigated the immune mechanisms underlying tumor regression toward the use of this bacterial vaccine in NMIBC patients. MB49 bladder tumor-bearing mice had significantly improved survival after intravesical instillations of Ty21a doses of 10 <sup>6</sup> to 10 <sup>8</sup> colony-forming units. By IHC and morphology, both BCG and Ty21a instillations were associated with bladder inflammation, which was decreased with the use of low, but effective doses of Ty21a. Flow-cytometry analysis showed a significant infiltration of T cells, natural killer (NK) cells, and myeloid cells, compared with controls, after a single dose of Ty21a, whereas this was only observed after multiple doses of BCG. The induced myeloid cells were predominantly neutrophils and Ly6C <sup>+</sup> CD103 <sup>+</sup> dendritic cells (DC), the latter being significantly more numerous after instillation of Ty21a than BCG. Ex vivo infection of human leukocytes with Ty21a, but not BCG, similarly significantly increased DC frequency. CD4 <sup>+</sup> and CD8 <sup>+</sup> T cells, but not NK cells nor neutrophils, were required for effective bladder tumor regression upon Ty21a treatment. Thus, the generation of antitumor adaptive immunity was identified as a key process underlying Ty21a-mediated treatment efficacy. Altogether, these results demonstrate mechanisms behind intravesical Ty21a therapy and suggest its potential as a safe and effective treatment for NMIBC patients.
Keywords
Administration, Intravesical, Animals, Cell Line, Tumor, Dendritic Cells/immunology, Disease Models, Animal, Female, Humans, Leukocytes/immunology, Mice, Mice, Inbred C57BL, Mycobacterium bovis, Polysaccharides, Bacterial/administration & dosage, Typhoid-Paratyphoid Vaccines/administration & dosage, Urinary Bladder Neoplasms/immunology, Urinary Bladder Neoplasms/therapy
Pubmed
Web of science
Open Access
Yes
Create date
25/02/2019 14:28
Last modification date
07/07/2020 6:20
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