Abstract 2783: The exosomes from cord blood stem cells, containing novel miRNAs, induce apoptosis in melanoma cells and enhance T cell anticancer function

Abstract

Abstract Regulatory T (Treg) cells expressing FOXP3 play a critical role in suppressing immune responses against anti-tumor immune responses. However, their presence in tumor tissues is often associated with poor prognosis. Cord blood stem cell-derived exosome vesicles (CBSC-EV) constitute a valuable source of lipids, microRNAs, and proteins, that are essential for cell-to-cell communication and provide therapeutic benefits. This study aimed to investigate the contents of CBSC-EV, identifying several known miRNAs (from Let7 and Let5 families) and two unknown miRNAs. Healthy lymphocytes, fibroblasts, and CHL1 amelanotic melanoma cell lines were transfected with these two novel miRNA inhibitors, and the changes before and after treatment compared to CBSC-EV and H2O2 were examined. Following treatment, the cells underwent a 24-hour incubation period, during which the level of cytotoxicity was assessed using CCK8, and the degree of DNA damage incurred was quantified with the Fast Microplate DNA damage assay. To further investigate the effects of treatment, RNA sequencing was conducted on both healthy and cancerous cells. The results demonstrated that CBSC-EV and novel miRNAs induced cytotoxicity in cancer cells, while in healthy cells, the DNA damage was repaired and cell viability was significantly increased (p<0.001). RNA sequencing revealed that following treatment with CBSC-EV and both CBSC-EV+N1 and N2 inhibitors in malignant melanoma cells, the expression of genes involved in the cytokine-mediated signaling pathway, cytokine-cytokine interaction, and cytokine activity were enhanced. In healthy cells treated with CBSC-EV and novel miRNA inhibitor transfection, the MT-CO1 gene was upregulated, contributing to cytochrome-c oxidase activity. This study presents evidence of the potential use of novel miRNAs as genetic material for cancer therapeutics in the future. Additionally, the findings suggest that these miRNAs could be used as an immune system modulator against melanoma. These findings demonstrate that miRNAs can effectively suppress resistance to anticancer cytotoxic therapy, which is a common feature of cancer cells. This suggests that miRNAs can potentially enhance current cancer therapies. Citation Format: Mojgan Mojgan Najafzadeh, Adi Baumgartner, Shohreh Jafarinejad, Zahra Karimi, Mohammad Isreb, Pouria Akhbari, Nader Ghaderi, Farshid Sefat, Saeed Heidari Keshel, Parisa Naeem, Rojan Ghaderi, Jacobo Elis Gomez, Diana Anderson, Andrew Wright. The exosomes from cord blood stem cells, containing novel miRNAs, induce apoptosis in melanoma cells and enhance T cell anticancer function [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2783.