Symbiosis between epithelial barriers and their microbial ecosystems has a major impact on local and systemic immune mechanisms, marked by influencing therapy response and clinical outcome in cancer patients. Gram+ and Gram- bacteria release bacterial extracellular vesicles (BEV), nanometer-sized membrane particles transporting nucleic acids, metabolites, proteins and endotoxins. We hypothesize that circulating BEV are, at least partially, responsible for the interaction between three biological entities: the microbiome, the tumor, and the immune system. I will focus on longitudinal blood plasma and stool samples from breast cancer (BC) and ovarian cancer (OC) patients to study circulating BEV since the chemotherapeutic efficacy for both cancer types is influenced by microbiota alterations. I will implement the in-house state-of-the-art expertise on BEV to: 1) Map the presence, abundance and composition of circulating and matched stool BEV; 2) Identify and associate the taxonomic classification of circulating and stool BEV with matched gut microbiota throughout the clinical course of cancer patients; 3) Clinically associate the presence, abundance and composition of circulating BEV with the tumor’s immune composition, systemic immune reaction, recurrence, chemotherapy effectiveness and toxicity. I am confident that understanding the contribution of circulating BEV to cancer progression and chemotherapy efficacy and toxicity can revolutionize patient management strategies.