Titre :

Cancer immunotherapies transition endothelial cells into HEVs that generate TCF1 ⁺ T lymphocyte niches through a feed-forward loop.

Auteur(s) :

Hua, Y. [Auteur]
Vella, G. [Auteur]
Rambow, F. [Auteur]
Allen, E. [Auteur]
Antoranz Martinez, A. [Auteur]
Duhamel, Marie [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192
Takeda, A. [Auteur]
Jalkanen, S. [Auteur]
Junius, S. [Auteur]
Smeets, A. [Auteur]
Nittner, D. [Auteur]
Dimmeler, S. [Auteur]
Hehlgans, T. [Auteur]
Liston, A. [Auteur]
Bosisio, F. M. [Auteur]
Floris, G. [Auteur]
Laoui, D. [Auteur]
Hollmén, M. [Auteur]
Lambrechts, D. [Auteur]
Merchiers, P. [Auteur]
Marine, J. C. [Auteur]
Schlenner, S. [Auteur]
Bergers, G. [Auteur]

Titre de la revue :

Cancer Cell

Nom court de la revue :

Cancer Cell

Date de publication :

2022-12-01

ISSN :

1878-3686

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

The lack of T cell infiltrates is a major obstacle to effective immunotherapy in cancer. Conversely, the formation of tumor-associated tertiary-lymphoid-like structures (TA-TLLSs), which are the local site of humoral ...
Lire la suite >The lack of T cell infiltrates is a major obstacle to effective immunotherapy in cancer. Conversely, the formation of tumor-associated tertiary-lymphoid-like structures (TA-TLLSs), which are the local site of humoral and cellular immune responses against cancers, is associated with good prognosis, and they have recently been detected in immune checkpoint blockade (ICB)-responding patients. However, how these lymphoid aggregates develop remains poorly understood. By employing single-cell transcriptomics, endothelial fate mapping, and functional multiplex immune profiling, we demonstrate that antiangiogenic immune-modulating therapies evoke transdifferentiation of postcapillary venules into inflamed high-endothelial venules (HEVs) via lymphotoxin/lymphotoxin beta receptor (LT/LTbR) signaling. In turn, tumor HEVs boost intratumoral lymphocyte influx and foster permissive lymphocyte niches for PD1 and PD1+ TCF1+ CD8 T cell progenitors that differentiate into GrzB+ PD1+ CD8 T effector cells. Tumor-HEVs require continuous CD8 and NK cellderived signals revealing that tumor HEV maintenance is actively sculpted by the adaptive immune system through a feed-forward loop.Lire moins >

Comité de lecture :

Oui

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

Université de Lille
Inserm
CHU Lille

Collections :

• Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192

Date de dépôt :

2023-12-13T03:59:04Z
2024-01-29T12:48:00Z