The pro-tumoral and anti-tumoral roles of EphA4 on T regulatory cells and tumor associated macrophages during HNSCC tumor progression DOI Open Access
Sophia Corbo, Diemmy Nguyen,

Shilpa Bhatia

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 13, 2024

Abstract Head and Neck Squamous Cell Carcinoma (HNSCC) is a deadly cancer with poor response to targeted therapy, largely driven by an immunosuppressive tumor microenvironment (TME). Here we examine the immune-modulatory role of receptor tyrosine kinase EphA4 in HNSCC progression. Within TME, primarily expressed on regulatory T cells (Tregs) macrophages. In contrast ephrinB2, activating ligand EphA4, blood vessels. Using genetically engineered mouse models, show that Tregs promotes growth, whereas monocytes inhibits growth. contrast, ephrinB2 knockout vessels reduces both intratumoral A novel specific inhibitor, APY-d3-PEG4, reverses accelerated growth had previously reported EphB4 cell knockout. macrophages not only enhanced their differentiation into M2 macrophage but also increased Treg suppressive activity. APY-d3-PEG4 reversed seen conferred no additional benefit when was knocked out Tregs. Underscoring EphA4-mediated interplay between macrophages, found decreases activation infiltration pro-tumoral These data identify as primary target suggest for regulating conversion. support possible anti-cancer therapeutic value bispecific peptides or antibodies capable promoting blockade Significance has effect while plays anti-tumoral underscoring necessity developing biologically rational therapeutics.

Language: Английский

Oxytocin lipidation expanding therapeutics for long-term reversal of autistic behaviors in rats DOI
Honglin Li, Ya Chen, Yue Qiu

et al.

International Journal of Pharmaceutics, Journal Year: 2025, Volume and Issue: unknown, P. 125299 - 125299

Published: Jan. 1, 2025

Language: Английский

Citations

0
Constrained β-Hairpins Targeting the EphA4 Ligand Binding Domain DOI Creative Commons

A.M. PRENTISS,

Carlo Baggio,

James Pagett

et al.

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 10, 2024

The activity of the receptor tyrosine kinase EphA4 has been implicated in several pathologies including oncology (gastric and pancreatic cancers) neurodegenerative diseases (amyotrophic lateral sclerosis Alzheimer's disease). However, advances validating as a possible drug target have limited by lack suitable pharmacological inhibitors. Recently, we reported on design potent agonistic agents targeting its ligand binding domain (LBD). Based previous studies with phage display cyclic peptide inhibitor, designed β-hairpin mimetic high affinity for EphA4-LBD. These hold great promise further validation development EphA4-based therapeutics. Moreover, our introduce strategy constrained peptides.

Language: Английский

Citations

0
The pro-tumoral and anti-tumoral roles of EphA4 on T regulatory cells and tumor associated macrophages during HNSCC tumor progression DOI Open Access
Sophia Corbo, Diemmy Nguyen,

Shilpa Bhatia

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 13, 2024

Abstract Head and Neck Squamous Cell Carcinoma (HNSCC) is a deadly cancer with poor response to targeted therapy, largely driven by an immunosuppressive tumor microenvironment (TME). Here we examine the immune-modulatory role of receptor tyrosine kinase EphA4 in HNSCC progression. Within TME, primarily expressed on regulatory T cells (Tregs) macrophages. In contrast ephrinB2, activating ligand EphA4, blood vessels. Using genetically engineered mouse models, show that Tregs promotes growth, whereas monocytes inhibits growth. contrast, ephrinB2 knockout vessels reduces both intratumoral A novel specific inhibitor, APY-d3-PEG4, reverses accelerated growth had previously reported EphB4 cell knockout. macrophages not only enhanced their differentiation into M2 macrophage but also increased Treg suppressive activity. APY-d3-PEG4 reversed seen conferred no additional benefit when was knocked out Tregs. Underscoring EphA4-mediated interplay between macrophages, found decreases activation infiltration pro-tumoral These data identify as primary target suggest for regulating conversion. support possible anti-cancer therapeutic value bispecific peptides or antibodies capable promoting blockade Significance has effect while plays anti-tumoral underscoring necessity developing biologically rational therapeutics.

Language: Английский

Citations

0