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Anti-PD-1 therapy triggers Tfh cell-dependent IL-4 release to boost CD8 T cell responses in tumor-draining lymph nodes.
Ruggiu, Mathilde; Guérin, Marion V; Corre, Béatrice; Bardou, Margot; Alonso, Ruby; Russo, Erica; Garcia, Zacarias; Feldmann, Lea; Lemaître, Fabrice; Dusseaux, Mathilde; Grandjean, Capucine L; Bousso, Philippe.
Afiliación
  • Ruggiu M; Institut Pasteur, Université de Paris Cité, INSERM U1223 , Paris, France.
  • Guérin MV; Institut Pasteur, Université de Paris Cité, INSERM U1223 , Paris, France.
  • Corre B; Institut Pasteur, Université de Paris Cité, INSERM U1223 , Paris, France.
  • Bardou M; Institut Pasteur, Université de Paris Cité, INSERM U1223 , Paris, France.
  • Alonso R; Institut Pasteur, Université de Paris Cité, INSERM U1223 , Paris, France.
  • Russo E; Institut Pasteur, Université de Paris Cité, INSERM U1223 , Paris, France.
  • Garcia Z; Institut Pasteur, Université de Paris Cité, INSERM U1223 , Paris, France.
  • Feldmann L; Institut Pasteur, Université de Paris Cité, INSERM U1223 , Paris, France.
  • Lemaître F; Institut Pasteur, Université de Paris Cité, INSERM U1223 , Paris, France.
  • Dusseaux M; Human Disease Models Core Facility, Institut Pasteur, Paris, France.
  • Grandjean CL; Institut Pasteur, Université de Paris Cité, INSERM U1223 , Paris, France.
  • Bousso P; Institut Pasteur, Université de Paris Cité, INSERM U1223 , Paris, France.
J Exp Med ; 221(4)2024 Apr 01.
Article en En | MEDLINE | ID: mdl-38417020
ABSTRACT
Anti-PD-1 therapy targets intratumoral CD8+ T cells to promote clinical responses in cancer patients. Recent evidence suggests an additional activity in the periphery, but the underlying mechanism is unclear. Here, we show that anti-PD-1 mAb enhances CD8+ T cell responses in tumor-draining lymph nodes by stimulating cytokine production in follicular helper T cells (Tfh). In two different models, anti-PD-1 mAb increased the activation and proliferation of tumor-specific T cells in lymph nodes. Surprisingly, anti-PD-1 mAb did not primarily target CD8+ T cells but instead stimulated IL-4 production by Tfh cells, the major population bound by anti-PD-1 mAb. Blocking IL-4 or inhibiting the Tfh master transcription factor BCL6 abrogated anti-PD-1 mAb activity in lymph nodes while injection of IL-4 complexes was sufficient to recapitulate anti-PD-1 mAb activity. A similar mechanism was observed in a vaccine model. Finally, nivolumab also boosted human Tfh cells in humanized mice. We propose that Tfh cells and IL-4 play a key role in the peripheral activity of anti-PD-1 mAb.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células T Auxiliares Foliculares / Neoplasias Límite: Animals / Humans Idioma: En Revista: J Exp Med Año: 2024 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células T Auxiliares Foliculares / Neoplasias Límite: Animals / Humans Idioma: En Revista: J Exp Med Año: 2024 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Estados Unidos