Immunomodulatory and antitumor effects of type I interferons and their application in cancer therapy

Autor(es)

Medrano, Ruan F. V. ; Hunger, Aline ; Mendonca, Samir Andrade ; Barbuto, Jose Alexandre M. ; Strauss, Bryan E.

• Tipo de documento: Artigo de Revisão
• Fonte: ONCOTARGET; v. 8, n. 41, p. 71249-71284, SEP 19 2017.
• Citações Web of Science: 25

Resumo

During the last decades, the pleiotropic antitumor functions exerted by type I interferons (IFNs) have become universally acknowledged, especially their role in mediating interactions between the tumor and the immune system. Indeed, type I IFNs are now appreciated as a critical component of dendritic cell (DC) driven T cell responses to cancer. Here we focus on IFN-alpha and IFN-beta, and their antitumor effects, impact on immune responses and their use as therapeutic agents. IFN-alpha/beta share many properties, including activation of the JAK-STAT signaling pathway and induction of a variety of cellular phenotypes. For example, type I IFNs drive not only the high maturation status of DCs, but also have a direct impact in cytotoxic T lymphocytes, NK cell activation, induction of tumor cell death and inhibition of angiogenesis. A variety of stimuli, including some standard cancer treatments, promote the expression of endogenous IFN-alpha/beta, which then participates as a fundamental component of immunogenic cell death. Systemic treatment with recombinant protein has been used for the treatment of melanoma. The induction of endogenous IFN-alpha/beta has been tested, including stimulation through pattern recognition receptors. Gene therapies involving IFN-alpha/beta have also been described. Thus, harnessing type I IFNs as an effective tool for cancer therapy continues to be studied. (AU)

• Processo FAPESP: 11/10656-5 - Avaliação dos mecanismos moleculares das vias de p53/ARF e IFN-beta envolvidos com a resposta de células de melanoma ao tratamento com os transgenes p19Arf e IFN-beta.
• Beneficiário: Aline Hunger Ribeiro
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 15/26580-9 - Terapia gênica do câncer: alinhamento estratégico para estudos translacionais
• Beneficiário: Bryan Eric Strauss
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 13/09474-5 - Associação da imunoterapia mediada pela transferência gênica de p19Arf e interferon-beta com morte imunogênica induzida pelo quimioterápico doxorrubicina para o tratamento do câncer
• Beneficiário: Ruan Felipe Vieira Medrano
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 13/25167-5 - Transferência gênica de p19Arf e interferon-beta: delineando a importância de sua combinação em modelos murinos de terapia gênica do câncer
• Beneficiário: Bryan Eric Strauss
• Modalidade de apoio: Auxílio à Pesquisa - Regular