Toll-like receptor 2 orchestrates a tumor suppressor response in non-small cell lung cancer.
CP: Cancer
SASP
Toll-like receptor
cancer therapy
innate immune receptors
non-small cell lung cancer
premalignancy
senescence
senescence surveillance
tumor suppressor
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
08 11 2022
08 11 2022
Historique:
received:
12
04
2022
revised:
08
09
2022
accepted:
12
10
2022
entrez:
9
11
2022
pubmed:
10
11
2022
medline:
15
11
2022
Statut:
ppublish
Résumé
Targeting early-stage lung cancer is vital to improve survival. However, the mechanisms and components of the early tumor suppressor response in lung cancer are not well understood. In this report, we study the role of Toll-like receptor 2 (TLR2), a regulator of oncogene-induced senescence, which is a key tumor suppressor response in premalignancy. Using human lung cancer samples and genetically engineered mouse models, we show that TLR2 is active early in lung tumorigenesis, where it correlates with improved survival and clinical regression. Mechanistically, TLR2 impairs early lung cancer progression via activation of cell intrinsic cell cycle arrest pathways and the proinflammatory senescence-associated secretory phenotype (SASP). The SASP regulates non-cell autonomous anti-tumor responses, such as immune surveillance of premalignant cells, and we observe impaired myeloid cell recruitment to lung tumors after Tlr2 loss. Last, we show that administration of a TLR2 agonist reduces lung tumor growth, highlighting TLR2 as a possible therapeutic target.
Identifiants
pubmed: 36351380
pii: S2211-1247(22)01461-9
doi: 10.1016/j.celrep.2022.111596
pmc: PMC10197427
mid: NIHMS1888916
pii:
doi:
Substances chimiques
Toll-Like Receptor 2
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
111596Subventions
Organisme : Cancer Research UK
ID : C47559/A16243
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 203913/Z/16/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : IS3-R1.07 20/21
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C157/A25140
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : R01 AG068048
Pays : United States
Organisme : NCI NIH HHS
ID : UG3 CA268103
Pays : United States
Organisme : Wellcome Trust
ID : 209710/Z/17/Z
Pays : United Kingdom
Organisme : Cancer Research UK
ID : A29576
Pays : United Kingdom
Informations de copyright
Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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