Introduction: Vascular abnormalities and immune suppressive characteristics of the tumour microenvironment represent a major obstacle in cancer immune therapy. Abnormal tumour vessels form a barrier that prevents effective blood flow, drug delivery and immune destruction. However, in a mouse model of neuroendocrine pancreatic cancer (RIP1-Tag5) we have previously shown that specific targeting of cytokines into tumours changes the inflammatory environment and the tumour vasculature to increase drug access and alleviate immune suppression. Methods: We produced a fusion protein consisting of the RGR peptide (CRGRRST) and tumour necrosis factor soluble factor 14 (TNFSF14/LIGHT) which specifically homes to angiogenic blood vessels in RIP1-Tag5 tumours. Intratumoural effects of LIGHT and its capacity to remodel tumour stroma were assessed after intravenous injections into tumour-bearing mice. Moreover, therapeutic efficacy of LIGHT in combination with immune therapy or cytotoxic drugs, which are ineffective as mono- therapies, were evaluated. Outcomes: We found that LIGHT when delivered into the tumour microenvironment shows dose dependent effects: High dose (2 ug) LIGHT destroys blood vessels and thus act similar to anti-angiogenic compounds. In contrast, minute amounts of LIGHT (0.2 ng) normalise the tumour vasculature and enhance tumour perfusion. This in turn increases penetration of cytotoxic drugs and anti-tumour CD8+ T cells during active immune therapy. Most strikingly, LIGHT at a dose of 20 ng induces formation of ectopic lymphoid structures in solid tumours, which support massive immune cell infiltration deep into the tumour parenchyma. Conclusions and recommendations: We provide proof-of-concept that the tumour stroma and vasculature are highly dynamic and can be remodelled by LIGHT in a dose-dependent manner. Overall, this encourages further development of combination therapies, which first create an angiostatic and immune stimulatory environment followed by cell lysis for complete tumour destruction.