RESUMEN
Triple-Negative Breast Cancer (TNBC) is one of the most aggressive and hot BC subtypes. Our research group has recently shed the light on the utility of natural compounds as effective immunotherapeutic agents. The aim of this study is to investigate the role of a methoxylated quercetin glycoside (MQG) isolated from Cleome droserifolia in harnessing TNBC progression and tuning the tumor microenvironment and natural killer cells cytotoxicity. Results showed that MQG showed the highest potency (IC50 = 12 µM) in repressing cellular proliferation, colony-forming ability, migration, and invasion capacities. Mechanistically, MQG was found to modulate a circuit of competing endogenous RNAs where it was found to reduce the oncogenic MALAT-1 lncRNA and induce TP53 and its downstream miRNAs; miR-155 and miR-146a. Accordingly, this leads to alteration in several downstream signaling pathways such as nitric oxide synthesizing machinery, natural killer cells' cytotoxicity through inducing the expression of its activating ligands such as MICA/B, ULBP2, CD155, and ICAM-1 and trimming of the immune-suppressive cytokines such as TNF-α and IL-10. In conclusion, this study shows that MQG act as a compelling anti-cancer agent repressing TNBC hallmarks, activating immune cell recognition, and alleviating the immune-suppressive tumor microenvironment experienced by TNBC patients.
Asunto(s)
Glicósidos/farmacología , MicroARNs/inmunología , ARN Largo no Codificante/inmunología , ARN Neoplásico/inmunología , Neoplasias de la Mama Triple Negativas/inmunología , Proteína p53 Supresora de Tumor/inmunología , Femenino , Humanos , Células MCF-7 , MicroARNs/genética , ARN Largo no Codificante/genética , ARN Neoplásico/genética , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/genética , Proteína p53 Supresora de Tumor/genéticaRESUMEN
The triple-negative subtype of breast cancer (TNBC) has the bleakest prognosis, owing to its lack of either hormone receptor as well as human epidermal growth factor receptor 2. Henceforth, immunotherapy has emerged as the front-runner for TNBC treatment, which avoids potentially damaging chemotherapeutics. However, despite its documented association with aggressive side effects and developed resistance, immune checkpoint blockade continues to dominate the TNBC immunotherapy scene. These immune checkpoint blockade drawbacks necessitate the exploration of other immunotherapeutic methods that would expand options for TNBC patients. One such method is the exploitation and recruitment of natural killer cells, which by harnessing the innate rather than adaptive immune system could potentially circumvent the downsides of immune checkpoint blockade. In this review, the authors will elucidate the advantageousness of natural killer cell-based immuno-oncology in TNBC as well as demonstrate the need to more extensively research such therapies in the future.