Publication: The coenzyme A precursor pantethine enhances antitumor immunity in sarcoma

Publié dans: Life Science Alliance, 2023, 6 (12), pp.e202302200. ⟨10.26508/lsa.202302200⟩

Auteurs: Richard Miallot, Virginie Millet, Anais Roger, Romain Fenouil, Catherine Tardivel, Jean-Charles Martin, Fabrice Tranchida, Laetitia Shintu, Paul Berchard, Juliane Sousa Lanza, Bernard Malissen, Sandrine Henri, Sophie Ugolini, Aurélie Dutour, Pascal Finetti, François Bertucci, Jean-Yves Blay, Franck Galland, Philippe Naquet

Résumé

We have previously identified the Vanin1 pathway as a tumor suppressor of sarcoma development via vitamin B5 and coenzyme A regeneration. Using an aggressive sarcoma cell line that lacks Vnn1 expression, we showed that the administration of pantethine, a vitamin B5 precursor, attenuates tumor growth in immunocompetent but not nude mice. Pantethine boosts antitumor immunity, including the polarization of myeloid and dendritic cells towards enhanced IFNγ-driven antigen presentation pathways and improved the development of hypermetabolic effector CD8 + T cells endowed with potential antitumor activity. At later stages of treatment, the effect of pantethine was limited by the development of immune cell exhaustion. Nevertheless, its activity was comparable with that of anti-PD1 treatment in sensitive tumors. In humans, VNN1 expression correlates with improved survival and immune cell infiltration in soft-tissue sarcomas, but not in osteosarcomas. Pantethine could be a potential therapeutic immunoadjuvant for the development of antitumor immunity.

Lien vers Pubmed [PMID] – 37833072

Lien vers HAL – cnrs-04374222

Lien vers le DOI – 10.26508/lsa.202302200