Study of immunotherapeutic effect of immunogenic cell death (ICD) by exosomes secreted from breast cancer cells under the influence of NLC containing Icilin

Abstract

Abstract: In cancer treatment, treatments that lead to immunogenic cell death or ICD are of great importance in stimulating the immune system against cancer. Factors secreted from dying cancer cells, such as DAMPs, stimulate the activation of immunogenic cell death against cancer. DAMPs can be secreted through active and passive methods or through exosomes. Exosomes are lipid bilayer nanoparticles (30-100 nm) that play an important role in intercellular communication between cancer cells and immune cells in the tumor microenvironment (TME). In different stressful and therapeutic conditions, the profile of secreted exosomal DAMPs changes and can play the role of stimulating or suppressing the immune system. Therefore, it is very important to pay attention to the changes in the profile of exosomes in different cancer treatment methods in the induction of ICD.

Method:: In this study, for the first time, changes in secreted exosomal DAMPs (CSP) from 4T1 breast cancer cells treated with icilin and hypothermia were investigated. Finally, to investigate their potential in inducing an immune response against cancer in the tumor microenvironment, 4T1 breast cancer tumors (as cold tumors) were induced in BALB/C mice, and after the injection of exosomes, the tumors were examined in terms of tumor volume. All factors examined for exosomes secreted from cells exposed to icilin (lipid nanoparticle containing icilin) were also investigated for hypothermia method as a non-nano method.

Results:The result showed that both methods enhanced exosome secretion and exosomal DAMPs—the injected exosomes which resulted in tumor growth inhibition. However, Lipid nanoparticles containing icilin-derived exosomes performed better than hypothermia in DAMPs expression and inhibiting tumor growth. In addition, the injection of the nanoparticle containing icilin also inhibited the growth of tumors so that in two of the mice, the tumor was completely removed.