RESUMO
NK cell cancer immunotherapy is an emerging anti-tumour therapeutic strategy that explores NK cell stimulation. In this review, we address strategies developed to circumvent limitations to clinical application of NK cell-based therapies, and comprehensively review the design and results of clinical trials conducted in the past 10 years (2008-2018) to test their therapeutic potential. NK cell-based immunotherapy of solid cancers remains controversial, but merit further detailed investigation.
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Imunoterapia Adotiva/métodos , Células Matadoras Naturais/transplante , Neoplasias/terapia , Ensaios Clínicos como Assunto , Humanos , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Neoplasias/imunologia , Neoplasias/patologia , Receptores de Superfície Celular/imunologia , Receptores de Superfície Celular/metabolismo , Projetos de Pesquisa , Transplante Homólogo , Resultado do TratamentoRESUMO
BACKGROUND: The aim of this study was to investigate the regulatory role of G-protein coupled receptor 120 (GPR120) in the development and progression of osteoarthritis (OA). METHODS: GPR120 knockout (KO) and wild-type (WT) mice were used to create an animal model of OA by means of anterior cruciate ligament transection (ACLT) surgery. The severity of OA was staged and evaluated by histological examination, microcomputed tomography scan and enzyme-linked immunosorbent assay (ELISA). The anti-inflammatory effects of the GPR120 agonist docosahexaenoic acid (DHA) on human chondrocytes were further evaluated by specific inflammatory markers. In addition, the healing progression of a skin defect model was determined with histological assays. RESULTS: The GPR120-KO mice displayed an accelerated development of OA after ACLT. The secondary inflammation, cartilage degeneration, and subchondral bone aberrant changes were significantly elevated in the early phase of OA in KO mice relative to those in WT mice. In addition, we found that GPR120 levels were downregulated in OA patients compared with control subjects, whereas GPR120 activation with DHA exhibited anti-inflammatory effects in primary human chondrocytes in vitro. Moreover, results from the skin defect model showed that GPR120 agonism with DHA enhanced wound repair in mice, as shown by the downregulation of the number of CD68+ cells. CONCLUSIONS: Our study suggests that GPR120 is an important inflammatory mediator during the development of OA, and that it is a potential marker for the diagnosis of high-risk patients with OA.