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Remodeling Fibrotic Tumor Microenvironment of Desmoplastic Melanoma to Facilitate Vaccine Immunotherapy

Abstract

Highly fibrotic and collagen-rich property in desmoplastic melanoma (DM) results in immune-suppressive fibrotic tumor microenvironment (TME) and resists to clinical therapies. The different clinical and pathological property compared to conventional melanoma leads to delayed diagnosis, and difficult to deliver drug effectively due to fibrosis. Here, we designed chemo-immuno strategy focused on combining vaccination immunotherapy with multi-targeting sunitinib (SUN) nano-therapy to remodel TME and generate a robust immune response and stronger synergistic anti-cancer effect. This strategy was evaluated side-by-side with non-desmoplastic melanoma and achieved significantly improvement of therapeutic efficacy. Here, the combination treatment synergistically was assessed with desmoplastic melanoma model. The strategy could remodel fibrotic immunosuppressive TME and result in a robust the cytotoxic T-cell response by reducing the collagen content, normalising blood vessels, inhibiting tumor-associated fibroblasts and reducing high levels of suppressor immune cells. The modification of fibrotic immunosuppressive TME may serve as a proposed approach to further enhance immunotherapy for desmoplastic tumors.

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Supplementary files

Article information


Submitted
11 Nov 2019
Accepted
31 Dec 2019
First published
08 Jan 2020

Nanoscale, 2020, Accepted Manuscript
Article type
Paper

Remodeling Fibrotic Tumor Microenvironment of Desmoplastic Melanoma to Facilitate Vaccine Immunotherapy

H. Zhu, Q. Liu, L. Miao, S. Musetti, M. Huo and L. Huang, Nanoscale, 2020, Accepted Manuscript , DOI: 10.1039/C9NR09610H

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