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Article Dans Une Revue Life Science Alliance Année : 2023

The coenzyme A precursor pantethine enhances antitumor immunity in sarcoma

Richard Miallot
Virginie Millet
  • Fonction : Auteur
Anais Roger
Romain Fenouil
  • Fonction : Auteur
Fabrice Tranchida
  • Fonction : Auteur
Laetitia Shintu
Paul Berchard
  • Fonction : Auteur
Juliane Sousa Lanza
  • Fonction : Auteur
Bernard Malissen
Sandrine Henri
Aurélie Dutour
François Bertucci
  • Fonction : Auteur
Jean-Yves Blay
Franck Galland
Philippe Naquet

Résumé

The tumor microenvironment is a dynamic network of stromal, cancer, and immune cells that interact and compete for resources. 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.

Dates et versions

hal-04423596 , version 1 (29-01-2024)

Identifiants

Citer

Richard Miallot, Virginie Millet, Anais Roger, Romain Fenouil, Catherine Tardivel, et al.. The coenzyme A precursor pantethine enhances antitumor immunity in sarcoma. Life Science Alliance, 2023, 6 (12), pp.e202302200. ⟨10.26508/lsa.202302200⟩. ⟨hal-04423596⟩
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