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De novo induction of intratumoral lymphoid structures and vessel normalization enhances immunotherapy in resistant tumors
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De novo induction of intratumoral lymphoid structures and vessel normalization enhances immunotherapy in resistant tumors
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Journal Article
De novo induction of intratumoral lymphoid structures and vessel normalization enhances immunotherapy in resistant tumors
2017
Overview
Ganss and colleagues show that targeting the inflammatory cytokine LIGHT to tumor vessels via a vascular targeting peptide induces tertiary lymphoid structures and enables the influx of endogenous T cells and tumor killing.
The tumor microenvironment confers profound resistance to anti-cancer immunotherapy. By targeting LIGHT, a member of the TNF superfamily of cytokines, to tumor vessels via a vascular targeting peptide (VTP), we developed a reagent with the dual ability to modulate the angiogenic vasculature and to induce tertiary lymphoid structures (TLSs). LIGHT-VTP triggered the influx of endogenous T cells into autochthonous or syngeneic tumors, which are resistant to immunotherapy. LIGHT-VTP in combination with checkpoint inhibition generated a large number of intratumoral effector and memory T cells with ensuing survival benefits, while the addition of anti-tumor vaccination achieved maximal therapeutic efficacy. Thus, the combination treatments stimulated the trafficking of pre-existing endogenous effector T cells as well as their intratumoral activation and were more successful than current immunotherapies, which fail due to tumor-intrinsic resistance mechanisms.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
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/ 13/2
/ 13/21
/ 13/51
/ 14/63
/ 38/1
/ 38/39
/ 38/77
/ 38/88
/ 38/90
/ 64/60
/ 82/80
/ 82/83
/ Animals
/ Cancer
/ Cancer Vaccines - administration & dosage
/ Cancer Vaccines - pharmacology
/ Drug Resistance, Neoplasm - immunology
/ Neovascularization, Pathologic - immunology
/ Neovascularization, Pathologic - therapy
/ Peptides
/ Peptides - administration & dosage
/ T cells
/ T-Lymphocytes - drug effects
/ Tumor Microenvironment - immunology
/ Tumor Necrosis Factor Ligand Superfamily Member 14 - chemistry
/ Tumor Necrosis Factor Ligand Superfamily Member 14 - genetics
/ Tumors
