Influence of Breast Cancer Extracellular Vesicles on Immune Cell Activation: A Pilot Study

Simple Summary The tumor microenvironment (TME) is a complex system composed of different cellular components that contribute to tumor growth and sustenance. The ability of the tumor to interact with the immune system through extracellular vesicles (EVs) represents a fundamental challenge for the scientific community to shed light on the intricate system that the tumor develops to escape the body's control. In our study, we investigate a possible specific immune cell activation towards releasing EVs and whether such activation could differ between different breast cancer subtypes or cellular 2D/3D model growth. Our data, although preliminary, aim to shed light on the effect of TME on the anti-tumor immune component to further develop personalized approaches in cancer diagnosis and treatment.Abstract Breast cancer is the leading cause of cancer-related death in women worldwide. It is well known that breast cancer shows significant alterations in the tumor microenvironment (TME), which is composed of a variety of immune cells, including natural killer (NK) cells, that have a key role in tumor development or anti-tumor responses in breast cancer patients. Luminal B (BT474) and triple-negative breast cancer (HS578T) cell lines were cultured in 2D and 3D model systems. PMBCs from healthy donors were isolated and treated with extracellular vesicles (EVs) from monolayer and spheroids of BT474 and HS578T and analyzed using cytofluorimetric approaches. We observed that EVs can alter the activation and presence of CD335+/CD11b+ NK cells. EVs derived from BT474 and HS578T cells trigger the activation and, simultaneously, a reduction in the percentage of CD335+/CD11b+ NK cells. In addition, EVs derived from BT474 also significantly reduce CD39+ T-regulatory (T-reg) cells. Our preliminary data suggest that using EVs to treat tumors could potentially alter components of the immune system, which causes hyperactivation of specific cell types and can lead to aggressive growth. These data will guide the designing of new personalized diagnostic approaches based on in-depth study of the TME.