A Critical Role for Fas-Mediated Off-Target Tumor Killing in T-cell Immunotherapy.
Animals
Antigens, Neoplasm
/ immunology
Bystander Effect
/ immunology
CD8-Positive T-Lymphocytes
/ immunology
CRISPR-Cas Systems
Cytotoxicity, Immunologic
Disease Models, Animal
Gene Editing
Genetic Engineering
Humans
Immunotherapy
/ adverse effects
Immunotherapy, Adoptive
/ adverse effects
Mice
Mice, Knockout
Neoplasms
/ etiology
Receptors, Chimeric Antigen
T-Cell Antigen Receptor Specificity
T-Lymphocytes
/ immunology
Treatment Outcome
Xenograft Model Antitumor Assays
fas Receptor
/ metabolism
Journal
Cancer discovery
ISSN: 2159-8290
Titre abrégé: Cancer Discov
Pays: United States
ID NLM: 101561693
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
received:
27
05
2020
revised:
11
10
2020
accepted:
19
11
2020
pubmed:
19
12
2020
medline:
20
1
2022
entrez:
18
12
2020
Statut:
ppublish
Résumé
T cell-based therapies have induced cancer remissions, though most tumors ultimately progress, reflecting inherent or acquired resistance including antigen escape. Better understanding of how T cells eliminate tumors will help decipher resistance mechanisms. We used a CRISPR/Cas9 screen and identified a necessary role for Fas-FasL in antigen-specific T-cell killing. We also found that Fas-FasL mediated off-target "bystander" killing of antigen-negative tumor cells. This localized bystander cytotoxicity enhanced clearance of antigen-heterogeneous tumors
Identifiants
pubmed: 33334730
pii: 2159-8290.CD-20-0756
doi: 10.1158/2159-8290.CD-20-0756
pmc: PMC7933082
mid: NIHMS1650124
doi:
Substances chimiques
Antigens, Neoplasm
0
Receptors, Chimeric Antigen
0
fas Receptor
0
Banques de données
ClinicalTrials.gov
['NCT02348216']
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
599-613Subventions
Organisme : NCI NIH HHS
ID : R37 CA246239
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI128949
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI113221
Pays : United States
Organisme : NCI NIH HHS
ID : R33 CA223947
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA154947
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA190400
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI007605
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA196521
Pays : United States
Organisme : Damon Runyon Cancer Research Foundation
ID : CI-76-14
Pays : United States
Organisme : NCCIH NIH HHS
ID : R01 AT011326
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007280
Pays : United States
Informations de copyright
©2020 American Association for Cancer Research.
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