Short-course radiotherapy promotes pro-inflammatory macrophages via extracellular vesicles in human rectal cancer

• DOI: 10.1136/jitc-2020-000667
• Publication Date: 2020-08-19T06:56:15Z
• Authors: Victoria Stary; Brigitte Wolf; Daniela Unterleut...; Julia List; Merjem Talic; Johannes Längle; Andrea Beer; Johanna Strobl; Georg Stary; Helmut Dolznig; Michael Bergmann, MD
• Keywords: Ex vivo; Macrophage polarization

Background Tumor-associated macrophages (TAM) constitute the most abundant immune cells in tumor stroma initiating pro-inflammatory (M1) or immunosuppressive (M2) responses depending on their polarization status. Advances immunotherapy call for a detailed understanding of potential immunogenic mechanisms irradiation routinely applied rectal cancer patients. Methods To test effects radiotherapy TAM, we ex vivo irradiated tissue samples human and assessed phenotype by flow cytometry. We furthermore evaluated distribution leucocyte subsets sections patients after short-course compared findings to non-pretreated using an immunostaining approach. Organotypic assays (OTA) consisting macrophages, cancer-associated fibroblast cell lines were used dissect immunological consequences macrophages. Results demonstrate that neoadjuvant is associated with shift TAM towards M1-like phenotype. In addition, caused increase phagocytic activity enhanced expression markers stimulatory signals necessary T-cell activation. OTA observed this alteration macrophage could be mediated extracellular vesicles (EV) derived from cells. identified high mobility group box 1 EV as effector signal crosstalk. Conclusions Our highlight upon diminishing activate pro-inflammation. data indicate clinically short-term may exploited stimulate suggest target status enhance future immunotherapeutic strategies.