Quantitative Interactomics in Primary T Cells Provides a Rationale for Concomitant PD-1 and BTLA Coinhibitor Blockade in Cancer Immunotherapy - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Cell Reports Année : 2019

Quantitative Interactomics in Primary T Cells Provides a Rationale for Concomitant PD-1 and BTLA Coinhibitor Blockade in Cancer Immunotherapy

Yunhao Zhai
  • Fonction : Auteur
  • PersonId : 1058043
Youcef Ounoughene
  • Fonction : Auteur
  • PersonId : 1058044

Résumé

Deciphering how TCR signals are modulated by coinhibitory receptors is of fundamental and clinical interest. Using quantitative interactomics, we define the composition and dynamics of the PD-1 and BTLA coinhibitory signalosomes in primary effector T cells and at the T cell-antigen-presenting cell interface. We also solve the existing controversy regarding the role of the SHP-1 and SHP-2 protein-tyrosine phosphatases in mediating PD-1 coinhibition. PD-1 predominantly recruits SHP-2, but when absent, it recruits SHP-1 and remains functional. In contrast, BTLA predominantly recruits SHP-1 and to a lesser extent SHP-2. By separately analyzing the PD-1-SHP-1 and PD-1-SHP-2 complexes, we show that both dampen the TCR and CD28 signaling pathways equally. Therefore, our study illustrates how comparison of coinhibitory receptor signaling via quantitative interactomics in primary T cells unveils their extent of redundancy and provides a rationale for designing combinations of blocking antibodies in cancer immunotherapy on the basis of undisputed modes of action.
Fichier principal
Vignette du fichier
S2211124719306618.pdf (11.77 Mo) Télécharger le fichier
Origine Fichiers produits par l'(les) auteur(s)

Dates et versions

hal-02359439 , version 1 (25-10-2021)

Licence

Identifiants

Citer

Javier Celis-Gutierrez, Peter Blattmann, Yunhao Zhai, Nicolas Jarmuzynski, Kilian Ruminski, et al.. Quantitative Interactomics in Primary T Cells Provides a Rationale for Concomitant PD-1 and BTLA Coinhibitor Blockade in Cancer Immunotherapy. Cell Reports, 2019, 27 (11), pp.3315+. ⟨10.1016/j.celrep.2019.05.041⟩. ⟨hal-02359439⟩
73 Consultations
12 Téléchargements

Altmetric

Partager

Gmail Mastodon Facebook X LinkedIn More