Adrenergic stress constrains the development of anti-tumor immunity and abscopal responses following local radiation.
Adrenergic Agents
/ pharmacology
Adrenergic beta-Antagonists
/ pharmacology
Animals
CD8-Positive T-Lymphocytes
/ drug effects
Cell Line, Tumor
Cell Proliferation
/ drug effects
Disease Models, Animal
Gene Expression Regulation, Neoplastic
/ drug effects
Immunity
Lymph Nodes
/ pathology
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Neoplasms
/ genetics
Radiation, Ionizing
Receptors, Adrenergic, beta-2
/ metabolism
Signal Transduction
/ drug effects
Stress, Physiological
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
14 04 2020
14 04 2020
Historique:
received:
12
06
2019
accepted:
18
03
2020
entrez:
15
4
2020
pubmed:
15
4
2020
medline:
22
7
2020
Statut:
epublish
Résumé
The abscopal effect following ionizing radiation therapy (RT) is considered to be a rare event. This effect does occur more frequently when combined with other therapies, including immunotherapy. Here we demonstrate that the frequency of abscopal events following RT alone is highly dependent upon the degree of adrenergic stress in the tumor-bearing host. Using a combination of physiologic, pharmacologic and genetic strategies, we observe improvements in the control of both irradiated and non-irradiated distant tumors, including metastatic tumors, when adrenergic stress or signaling through β-adrenergic receptor is reduced. Further, we observe cellular and molecular evidence of improved, antigen-specific, anti-tumor immune responses which also depend upon T cell egress from draining lymph nodes. These data suggest that blockade of β2 adrenergic stress signaling could be a useful, safe, and feasible strategy to improve efficacy in cancer patients undergoing radiation therapy.
Identifiants
pubmed: 32286326
doi: 10.1038/s41467-020-15676-0
pii: 10.1038/s41467-020-15676-0
pmc: PMC7156731
doi:
Substances chimiques
Adrenergic Agents
0
Adrenergic beta-Antagonists
0
Receptors, Adrenergic, beta-2
0
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
1821Subventions
Organisme : NCI NIH HHS
ID : P30 CA016056
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA099326
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA205246
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA236390
Pays : United States
Organisme : NCI NIH HHS
ID : F32 CA239356
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA229812
Pays : United States
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