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Small Molecule Inhibition of Glycogen Synthase Kinase-3 in Cancer Immunotherapy.
Adv Exp Med Biol ; 1164: 225-233, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31576552
ABSTRACT
Immune checkpoint blockade (ICB) has proved successful in the immunotherapeutic treatment of various human cancers. Despite its success, most patients are still not cured while immunogenic cold cancers are still poorly responsive. There is a need for novel clinical interventions in immunotherapy, either alone or in conjunction with ICB. Here, we outline our recent discovery that the intracellular signaling kinase glycogen synthase kinase-3 (GSK-3) is a central regulator of PD-1 in T-cells. We demonstrate the application of small molecule inhibitor (SMI) approaches to down-regulate PD-1 in tumor immunotherapy. GSK-3 SMIs were found as effective as anti-PD-1 in the elimination of melanoma in mouse models. We propose the development of novel SMIs to target co-receptors for the future of immunotherapy.
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Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Assunto principal: Regulação Neoplásica da Expressão Gênica / Quinase 3 da Glicogênio Sintase / Imunoterapia / Melanoma Limite: Animais / Humanos Idioma: Inglês Revista: Adv Exp Med Biol Ano de publicação: 2019 Tipo de documento: Artigo País de afiliação: Reino Unido