Intratumoral Tcf1+PD-1+CD8+ T Cells with Stem-like Properties Promote Tumor Control in Response to Vaccination and Checkpoint Blockade Immunotherapy.

Fiche du document

Auteurs
Date

15 janvier 2019

Type de document
Périmètre
Langue
Identifiants
Source

Serveur académique Lausannois

Relations

Ce document est lié à :
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.immuni.2018.12.021

Ce document est lié à :
info:eu-repo/semantics/altIdentifier/pmid/30635237

Ce document est lié à :
info:eu-repo/semantics/altIdentifier/eissn/1097-4180

Ce document est lié à :
info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_8DBCBF3E53B57

Collection

Serveur Académique Lausannois

Organisation

Université de Lausanne et CHUV

Licences

info:eu-repo/semantics/openAccess , CC BY-NC-ND 4.0 , https://creativecommons.org/licenses/by-nc-nd/4.0/

Mots-clés 0

Animals; Antibodies, Monoclonal/therapeutic use; CD8-Positive T-Lymphocytes/drug effects; CD8-Positive T-Lymphocytes/immunology; Cell Differentiation; Cell Proliferation; Hepatitis A Virus Cellular Receptor 2/antagonists & inhibitors; Hepatocyte Nuclear Factor 1-alpha/genetics; Hepatocyte Nuclear Factor 1-alpha/metabolism; Humans; Immunotherapy; Lymphocytes, Tumor-Infiltrating/drug effects; Lymphocytes, Tumor-Infiltrating/immunology; Melanoma/immunology; Melanoma/therapy; Melanoma, Experimental; Mice; Mice, Inbred C57BL; Programmed Cell Death 1 Receptor/antagonists & inhibitors; Stem Cells/immunology; T-Lymphocyte Subsets/immunology; T cell exhaustion; T cell factor 1; T cell reinvigoration; cancer immunotherapy; checkpoint blockade; memory-like T cells; stem-like T cells; therapeutic vaccination

Sujets proches En

Thymus-dependent lymphocytes Thymus-derived cells T lymphocytes Thymus-dependent cells

Citer ce document

I. Siddiqui et al., « Intratumoral Tcf1+PD-1+CD8+ T Cells with Stem-like Properties Promote Tumor Control in Response to Vaccination and Checkpoint Blockade Immunotherapy. », Serveur académique Lausannois, ID : 10.1016/j.immuni.2018.12.021

Métriques

Partage / Export

Résumé 0

Checkpoint blockade mediates a proliferative response of tumor-infiltrating CD8 + T lymphocytes (TILs). The origin of this response has remained elusive because chronic activation promotes terminal differentiation or exhaustion of tumor-specific T cells. Here we identified a subset of tumor-reactive TILs bearing hallmarks of exhausted cells and central memory cells, including expression of the checkpoint protein PD-1 and the transcription factor Tcf1. Tcf1 + PD-1 + TILs mediated the proliferative response to immunotherapy, generating both Tcf1 + PD-1 + and differentiated Tcf1 - PD-1 + cells. Ablation of Tcf1 + PD-1 + TILs restricted responses to immunotherapy. Tcf1 was not required for the generation of Tcf1 + PD-1 + TILs but was essential for the stem-like functions of these cells. Human TCF1 + PD-1 + cells were detected among tumor-reactive CD8 + T cells in the blood of melanoma patients and among TILs of primary melanomas. Thus, immune checkpoint blockade relies not on reversal of T cell exhaustion programs, but on the proliferation of a stem-like TIL subset.

document thumbnail

Par les mêmes auteurs

Sur les mêmes sujets

Exporter en