RESUMEN
PLK1 (Polo-like kinase 1) plays a critical role in the progression of lung adenocarcinoma (LUAD). Recent studies have unveiled that targeting PLK1 improves the efficacy of immunotherapy, highlighting its important role in the regulation of tumor immunity. Nevertheless, our understanding of the intricate interplay between PLK1 and the tumor microenvironment (TME) remains incomplete. Here, using genetically engineered mouse model and single-cell RNA-seq analysis, we report that PLK1 promotes an immunosuppressive TME in LUAD, characterized with enhanced M2 polarization of tumor associated macrophages (TAM) and dampened antigen presentation process. Mechanistically, elevated PLK1 coincides with increased secretion of CXCL2 cytokine, which promotes M2 polarization of TAM and diminishes expression of class II major histocompatibility complex (MHC-II) in professional antigen-presenting cells. Furthermore, PLK1 negatively regulates MHC-II expression in cancer cells, which has been shown to be associated with compromised tumor immunity and unfavorable patient outcomes. Taken together, our results reveal PLK1 as a novel modulator of TME in LUAD and provide possible therapeutic interventions.
Asunto(s)
Adenocarcinoma del Pulmón , Proteínas de Ciclo Celular , Neoplasias Pulmonares , Quinasa Tipo Polo 1 , Proteínas Serina-Treonina Quinasas , Proteínas Proto-Oncogénicas , Análisis de la Célula Individual , Microambiente Tumoral , Animales , Humanos , Ratones , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/inmunología , Adenocarcinoma del Pulmón/patología , Presentación de Antígeno/genética , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Línea Celular Tumoral , Quimiocina CXCL2/genética , Quimiocina CXCL2/metabolismo , Regulación Neoplásica de la Expresión Génica , Antígenos de Histocompatibilidad Clase II/genética , Antígenos de Histocompatibilidad Clase II/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/patología , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas/metabolismo , Microambiente Tumoral/inmunología , Microambiente Tumoral/genética , Macrófagos Asociados a Tumores/inmunología , Macrófagos Asociados a Tumores/metabolismoRESUMEN
Frailty is a condition in which the affected individual is more prone to both external and internal stressors and has a higher risk of succumbing to chronic diseases. The aim of this research was to translate and validate the PRISMA-7 questionnaire in the Urdu language. This is a validation study conducted in a hospital in Khyber Pakhtunkhwa, Pakistan. PRISMA-7 Questionnaire was translated into Urdu language using forward and backward translations and was then piloted on a sample of 151 subjects, aged 60 and above, and validated by applying reliability and validity statistics. Amongst the sampling population, frailty was found to be 63.26%. All the items in the questionnaire were significantly different from each other, however, the correlation between each was found to be low. Cronbach's alpha was found to be 0.322. Urdu translated version of PRISMA-7 is not a valid and reliable tool for screening frailty in the elderly population of Khyber Pakhtunkhwa, Pakistan. Key Words: Frailty, Validation, Translation, Frail elderly, Urdu.