Article Dans Une Revue Cancer Immunology Research Année : 2021

MHC Class II Antigen Presentation by Lymphatic Endothelial Cells in Tumors Promotes Intratumoral Regulatory T cell–Suppressive Functions

Anastasia Gkountidi
  • Fonction : Auteur
Laure Garnier
  • Fonction : Auteur
Juan Dubrot
  • Fonction : Auteur
Julien Angelillo
Dale Brighouse
Ludovic Wrobel
Robert Pick
Christoph Scheiermann
  • Fonction : Auteur
Melody Swartz
  • Fonction : Auteur
Stéphanie Hugues
  • Fonction : Auteur

Résumé

Abstract Several solid malignancies trigger lymphangiogenesis, facilitating metastasis. Tumor-associated lymphatic vessels significantly contribute to the generation of an immunosuppressive tumor microenvironment (TME). Here, we have investigated the ability of tumoral lymphatic endothelial cells (LEC) to function as MHC class II–restricted antigen-presenting cells in the regulation of antitumor immunity. Using murine models of lymphangiogenic tumors engrafted under the skin, we have shown that tumoral LECs upregulate MHC class II and the MHC class II antigen-processing machinery, and that they promote regulatory T-cell (Treg) expansion ex vivo. In mice with LEC-restricted lack of MHC class II expression, tumor growth was severely impaired, whereas tumor-infiltrating effector T cells were increased. Reduction of tumor growth and reinvigoration of tumor-specific T-cell responses both resulted from alterations of the tumor-infiltrating Treg transcriptome and phenotype. Treg-suppressive functions were profoundly altered in tumors lacking MHC class II in LECs. No difference in effector T-cell responses or Treg phenotype and functions was observed in tumor-draining lymph nodes, indicating that MHC class II–restricted antigen presentation by LECs was required locally in the TME to confer potent suppressive functions to Tregs. Altogether, our study suggests that MHC class II–restricted antigen-presenting tumoral LECs function as a local brake, dampening T cell–mediated antitumor immunity and promoting intratumoral Treg-suppressive functions.

Dates et versions

hal-03925764 , version 1 (05-01-2023)

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Citer

Anastasia Gkountidi, Laure Garnier, Juan Dubrot, Julien Angelillo, Guillaume Harlé, et al.. MHC Class II Antigen Presentation by Lymphatic Endothelial Cells in Tumors Promotes Intratumoral Regulatory T cell–Suppressive Functions. Cancer Immunology Research, 2021, 9 (7), pp.748-764. ⟨10.1158/2326-6066.CIR-20-0784⟩. ⟨hal-03925764⟩
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