TUSC2 immunogene enhances efficacy of chemo-immuno combination on KRAS/LKB1 mutant NSCLC in humanized mouse model.
AMP-Activated Protein Kinases
/ genetics
Animals
Antibodies, Monoclonal, Humanized
/ administration & dosage
Antineoplastic Combined Chemotherapy Protocols
/ pharmacology
Carboplatin
/ administration & dosage
Carcinoma, Non-Small-Cell Lung
/ drug therapy
Disease Models, Animal
Genes, Tumor Suppressor
Lung Neoplasms
/ drug therapy
Mice
Proto-Oncogene Proteins p21(ras)
/ genetics
Tumor Microenvironment
Tumor Suppressor Proteins
/ genetics
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
24 02 2022
24 02 2022
Historique:
received:
22
08
2021
accepted:
01
02
2022
entrez:
25
2
2022
pubmed:
26
2
2022
medline:
5
4
2022
Statut:
epublish
Résumé
KRAS/LKB1 (STK11) NSCLC metastatic tumors are intrinsically resistant to anti-PD-1 or PD-L1 immunotherapy. In this study, we use a humanized mouse model to show that while carboplatin plus pembrolizumab reduce tumor growth moderately and transiently, the addition of the tumor suppressor gene TUSC2, delivered systemically in nanovesicles, to this combination, eradicates tumors in the majority of animals. Immunoprofiling of the tumor microenvironment shows the addition of TUSC2 mediates: (a) significant infiltration of reconstituted human functional cytotoxic T cells, natural killer cells, and dendritic cells; (b) induction of antigen-specific T cell responses; (c) enrichment of functional central and memory effector T cells; and (d) decreased levels of PD-1
Identifiants
pubmed: 35210547
doi: 10.1038/s42003-022-03103-7
pii: 10.1038/s42003-022-03103-7
pmc: PMC8873264
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Tumor Suppressor Proteins
0
Tusc2 protein, mouse
0
Carboplatin
BG3F62OND5
pembrolizumab
DPT0O3T46P
Stk11 protein, mouse
EC 2.7.11.1
AMP-Activated Protein Kinases
EC 2.7.11.31
Hras protein, mouse
EC 3.6.5.2
Proto-Oncogene Proteins p21(ras)
EC 3.6.5.2
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
167Subventions
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA070907
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA224065
Pays : United States
Informations de copyright
© 2022. The Author(s).
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