RESUMEN
Incomplete radiofrequency ablation (IRFA) triggers mild protective autophagy in residual tumor cells and results in an immunosuppressive microenvironment. This accelerates the recurrence of residual tumors and causes resistance to anti-PD-1/PDL1 therapy, which bringing a great clinical challenge in residual tumors immunotherapy. Mild autophagy activation can promote cancer cell survival while further amplification of autophagy contributes to immunogenic cell death (ICD). To this regard, we constructed active targeting zeolitic imidazolate framework-8 (ZIF-8) nanoparticles (NPs) loaded with STF62247 or both STF62247 and BMS202, namely STF62247@ZIF-8/PEG-FA (SZP) or STF62247-BMS202@ZIF-8/PEG-FA (SBZP) NPs. We found that SZP NPs inhibited proliferation and stimulated apoptosis of residual tumor cells exposed to sublethal heat stress in an autophagy-dependent manner. Further results discovered that SZP NPs could amplify autophagy in residual tumor cells and evoke their ICD, which dramatically boosted the maturation of dendritic cells (DCs). Through vaccination experiments, we found for the first time that vaccination with heat + SZP treatment could efficiently suppress the growth of new tumors and establish long-term immunological memory. Furthermore, SBZP NPs could remarkably promote the ICD of residual tumor cells, obviously activate the anti-tumor immune microenvironment, and significantly inhibit the growth of residual tumors. Thus, amplified autophagy coupled with anti-PD-1/PDL1 therapy is potentially a novel strategy for treating residual tumors after IRFA.
Asunto(s)
Neoplasias Hepáticas , Nanopartículas , Humanos , Neoplasias Hepáticas/patología , Neoplasia Residual , Línea Celular Tumoral , Muerte Celular Inmunogénica , Antígeno B7-H1 , Inmunoterapia , Autofagia , Microambiente TumoralRESUMEN
OBJECTIVES: Transcatheter closure has become one of the main treatment methods for patent foramen ovale (PFO). However, the population in southern China is generally thin and the size of PFO is small, so the application of minimalist surgery is challenging. This study aimed to analyze the morphological characteristics of PFOs in southern China by transesophageal echocardiography (TEE), and to explore the influence on minimalist transcatheter closure. METHODS: About 110 patients with PFO closure in our hospital were selected. All cases were examined by TEE including the PFO size, length, septum secundum thickness, color characteristic and surrounding structures, and morphologically classified. During the operation, the procedure time, number of times for the guidewire attempting to pass the interatrial septum and the success rate of simply using J guidewire to cross the interatrial septum were recorded. RESULTS: About 110 cases of PFO were classified into two categories and four subtypes, including 55 cases with Uniform Channel Type (UCT, 50.0%), 16 cases with Irregular Channel Type (ICT, 14.6%), 15 cases with Right Funnel Type (RFT, 13.6%), and 24 cases with Left Funnel Type (LFT, 21.8%). According to the complexity of the procedure, they were divided into simple procedure (n = 73) and complex procedure (n = 37). Multivariate logistic regression showed that the anatomical types of PFO, the tunnel entrance size, and the tunnel entrance size <2 mm were independent factors affecting the complexity of procedure [OR = 2.819, 95% CI (1.124, 7.066), p = .027; OR = .027, 95% CI (.004, .208), p = .001; OR = 4.715, 95% CI (1.028, 21.619), p = .046]. With ICT and LFT groups, the procedure duration was relatively long (p < .001), number of times for the guidewire attempting to pass the interatrial septum was significantly increased (p < .001), and the success rate of simply using J guidewire to cross the interatrial septum was relatively low (p < .001). CONCLUSIONS: The PFO size in southern China was relatively small and characterized by large tunnel tension. It was concluded that TEE could clearly show the morphological characteristics of PFO, which could provide guidance for making more reasonable surgical plans in clinical practice, shorten the procedure time and improve the success rate of PFO closure.