Intratumoral LIGHT Restores Pericyte Contractile Properties and Vessel Integrity

• DOI: 10.1016/j.celrep.2015.12.004
• Publication Date: 2015-12-19T01:36:08Z
• Authors: Anna Johansson-Pe...; Zhi-Jie Li; Devina D. Lakhiani; Bo He; Xiao Wang; Juliana Hamzah; Ruth Ganss
• Keywords: Pericyte; Structural integrity

Highlights•LIGHT targeting into tumors normalizes the vasculature and improves therapy•Vascular integrity is restored by inducing pericyte contractility•LIGHT triggers a peri-vascular signaling cascade involving macrophages TGF-β•LIGHT-RGR effects are Rho kinase-dependent restricted to vascular bedSummaryNormalization of tumor an emerging concept shown improve anti-cancer therapy. However, there currently no clinical interventions that effect long-lasting normalization. Here, we have developed strategy for normalization specific intratumoral delivery LIGHT/TNFSF14. Importantly, occurs induced expression contractile markers in pericytes, which turn re-establishes tight pericyte-vessel alignment. Restoring vessel perfusion acts as adjuvant chemo- immunotherapy. Mechanistically, LIGHT induces differentiation via kinase signaling. Minute amounts act paracrine fashion trigger amplifying transforming growth factor β (TGF-β) from macrophages. That these can be reproduced adoptive transfer LIGHT-stimulated alone demonstrates their central role regulating differentiation. Our findings highlight crucial properties normalization, effected macrophage signaling, thus providing so far unexplored opportunities.Graphical abstract