Background and aims: Malignant melanoma is an aggressive tumor sensitive for immunotherapy such as checkpoint\nblockade antibodies. Still, most patients with late stage disease do not respond, and the side effects can be\nsevere. Stimulation of the CD40 pathway to initiate anti-tumor immunity is a promising alternative. Herein, we demonstrate\nimmune profiling data from melanoma patients treated with an adenovirus-based CD40 ligand gene therapy\n(AdCD40L).\nMethods: Peripheral blood mononuclear cells and plasma were collected from malignant melanoma patients\n(n = 15) enrolled in a phase I/IIa study investigating intratumoral delivery of AdCD40L with or without low dose\ncyclophosphamide. Cells were analyzed by flow cytometry while plasma samples were analyzed by a multi-array\nproteomics.\nResults: All patients had an increased Teffector/Tregulatory cell ratio post therapy. Simultaneously, the death receptors\nTNFR1 and TRAIL-R2 were significantly up-regulated post treatment. Stem cell factor (SCF), E-selectin, and CD6\ncorrelated to enhanced overall survival while a high level of granulocytic myeloid-derived suppressor cells (gMDSCs),\nIL8, IL10, TGFb1, CCL4, PlGF and Fl3t ligand was highest in patients with short survival.\nConclusions: AdCD40L intratumoral injection induced desirable systemic immune effects that correlated to prolonged\nsurvival. Further studies using CD40 stimulation in malignant melanoma are warranted.
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