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ResearchIn-Press PreviewOncologyTherapeutics Open Access | 10.1172/JCI176748
1Department of Dermatology, The University of Texas Southwestern Medical Center, Dallas, United States of America
2Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, United States of America
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1Department of Dermatology, The University of Texas Southwestern Medical Center, Dallas, United States of America
2Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, United States of America
Find articles by Madana, L. in: JCI | PubMed | Google Scholar
1Department of Dermatology, The University of Texas Southwestern Medical Center, Dallas, United States of America
2Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, United States of America
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1Department of Dermatology, The University of Texas Southwestern Medical Center, Dallas, United States of America
2Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, United States of America
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1Department of Dermatology, The University of Texas Southwestern Medical Center, Dallas, United States of America
2Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, United States of America
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1Department of Dermatology, The University of Texas Southwestern Medical Center, Dallas, United States of America
2Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, United States of America
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1Department of Dermatology, The University of Texas Southwestern Medical Center, Dallas, United States of America
2Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, United States of America
Find articles by Le, L. in: JCI | PubMed | Google Scholar |
Published March 19, 2024 - More info
Neurofibromatosis Type 1 (NF1) is caused by mutations in the NF1 gene that encodes neurofibromin, a RAS GTPase-Activating Protein. Inactivating NF1 mutations cause hyperactivation of RAS-mediated signaling, resulting in development of multiple neoplasms, including Malignant Peripheral Nerve Sheath Tumors (MPNSTs). MPNSTs are an aggressive tumor and the main cause of mortality in NF1 patients. MPNSTs are difficult to resect and refractory to chemo- and radiotherapy, and no molecular therapies currently exist. Immune Checkpoint Blockade (ICB) is an approach to treat inoperable, undruggable cancers like MPNST, but successful outcomes require an immune cell-rich tumor microenvironment (TME). While MPNSTs are non-inflamed “cold” tumors, here, we turned MPNSTs into T cell-inflamed “hot” tumors by activating “stimulator of interferon genes” (STING) signaling. Mouse genetic and human xenograft MPNST models treated with STING agonist plus ICB exhibited growth delay via increased apoptotic cell death. This strategy offers a potential treatment regimen for MPNST.