RESUMEN
Immune checkpoint blockade (ICB) therapy is an important treatment option for individuals with cancer, but it has certain limitations. Identifying a better target that can overcome tumor immune escape and stimulate T cell activity is critical. This research aimed to delve into the molecular mechanism underlying the immunoregulatory function of metadherin (MTDH), which is a novel and potential therapeutic target in hepatocellular cancer (HCC). A small interfering RNA library was screened using the luciferase reporter assay and PD-L1 promoter. The Cancer Genome Atlas database and HCC tissues were used to investigate the relationship between MTDH and PD-L1. The association between MTDH and ß-catenin/lymphoid enhancer binding factor (LEF-1) was discovered by co-immunoprecipitation. The chromatin immunoprecipitation assay was used to investigate the interaction of MTDH with the PD-L1 promoter when LEF-1 expression was silenced. Locked nucleic acid antisense oligonucleotides (ASOs) were used to inhibit MTDH. We utilized in vitro co-cultures and in vivo syngeneic tumor development experiments to confirm the effectiveness of MTDH ASO combined with PD-1 monoclonal antibody (mAb). MTDH was demonstrated to be a PD-L1 modulator. MTDH increased PD-L1 expression and upregulated PD-L1 transcriptional activity through ß-catenin/LEF-1 signaling. More importantly, MTDH ASO improved the anti-PD-1 response and increased cytotoxic T-cell infiltration in PD-1 mAb-treated malignancies. MTDH effectively predicts the therapeutic efficacy of ICB therapy. Our results imply that combining MTDH ASO with PD-1 mAb could be a promising therapeutic strategy for HCC. In addition, MTDH is a potential novel biomarker for predicting the effectiveness of immune checkpoint inhibitor treatment.
Asunto(s)
Anticuerpos Monoclonales , Antígeno B7-H1 , Carcinoma Hepatocelular , Inhibidores de Puntos de Control Inmunológico , Neoplasias Hepáticas , Proteínas de la Membrana , Oligonucleótidos Antisentido , Proteínas de Unión al ARN , Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales/farmacología , Antígeno B7-H1/antagonistas & inhibidores , Antígeno B7-H1/genética , Antígeno B7-H1/inmunología , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/inmunología , Línea Celular Tumoral , Humanos , Inhibidores de Puntos de Control Inmunológico/farmacología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/inmunología , Proteínas de la Membrana/genética , Proteínas de la Membrana/inmunología , Oligonucleótidos Antisentido/inmunología , Receptor de Muerte Celular Programada 1/metabolismo , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/inmunología , Microambiente Tumoral , beta Catenina/genética , beta Catenina/inmunologíaRESUMEN
PURPOSE: During the survival period of breast cancer patients, an understanding of and ability to implement health knowledge may be important for survivors' physical and mental quality of life (QOL). This study aims to investigate the health literacy and predictors of QOL for survivors of breast cancer. METHOD: A cross-sectional design was used, and convenience sampling was performed. Eighty-six survivors with breast cancer were recruited from a general hospital in northern Taiwan from February to August 2017. Taiwan's health literacy scale and SF-12 questionnaire were used for data collection. RESULTS: The average health literacy score was 3.28. Education level and breast cancer stage were significant factors for the health literacy of survivors with breast cancer. Age, body mass index and health literacy were predictors of physical health-related QOL. Health literacy also was a predictor of mental health-related QOL. CONCLUSION: The results provide the factors associated health literacy as well as health-related QOL. Nurses should understand the health literacy among survivors with breast cancer and improve health literacy to optimize their quality of life.