hMENA isoforms regulate cancer intrinsic type I IFN signaling and extrinsic mechanisms of resistance to immune checkpoint blockade in NSCLC.
biomarkers, tumor
cytokines
immune checkpoint inhibitors
macrophages
non-small cell lung cancer
Journal
Journal for immunotherapy of cancer
ISSN: 2051-1426
Titre abrégé: J Immunother Cancer
Pays: England
ID NLM: 101620585
Informations de publication
Date de publication:
08 2023
08 2023
Historique:
accepted:
08
08
2023
medline:
25
8
2023
pubmed:
24
8
2023
entrez:
23
8
2023
Statut:
ppublish
Résumé
Understanding how cancer signaling pathways promote an immunosuppressive program which sustains acquired or primary resistance to immune checkpoint blockade (ICB) is a crucial step in improving immunotherapy efficacy. Among the pathways that can affect ICB response is the interferon (IFN) pathway that may be both detrimental and beneficial. The immune sensor retinoic acid-inducible gene I (RIG-I) induces IFN activation and secretion and is activated by actin cytoskeleton disturbance. The actin cytoskeleton regulatory protein hMENA, along with its isoforms, is a key signaling hub in different solid tumors, and recently its role as a regulator of transcription of genes encoding immunomodulatory secretory proteins has been proposed. When hMENA is expressed in tumor cells with low levels of the epithelial specific hMENA Effects of hMENA Transcriptomic and biochemical analyses demonstrated that the depletion of hMENA Collectively, these data establish a new function for the actin cytoskeleton regulator hMENA
Sections du résumé
BACKGROUND
Understanding how cancer signaling pathways promote an immunosuppressive program which sustains acquired or primary resistance to immune checkpoint blockade (ICB) is a crucial step in improving immunotherapy efficacy. Among the pathways that can affect ICB response is the interferon (IFN) pathway that may be both detrimental and beneficial. The immune sensor retinoic acid-inducible gene I (RIG-I) induces IFN activation and secretion and is activated by actin cytoskeleton disturbance. The actin cytoskeleton regulatory protein hMENA, along with its isoforms, is a key signaling hub in different solid tumors, and recently its role as a regulator of transcription of genes encoding immunomodulatory secretory proteins has been proposed. When hMENA is expressed in tumor cells with low levels of the epithelial specific hMENA
METHODS
Effects of hMENA
RESULTS
Transcriptomic and biochemical analyses demonstrated that the depletion of hMENA
CONCLUSIONS
Collectively, these data establish a new function for the actin cytoskeleton regulator hMENA
Identifiants
pubmed: 37612043
pii: jitc-2023-006913
doi: 10.1136/jitc-2023-006913
pmc: PMC10450042
pii:
doi:
Substances chimiques
Immune Checkpoint Inhibitors
0
Interferon Type I
0
Protein Isoforms
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: None declared.
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