Williford, John-MichaelIshihara, JunIshihara, AkoMansurov, AslanHosseinchi, PeymanMarchell, Tiffany M.Potin, LambertSwartz, Melody A.Hubbell, Jeffrey A.2020-01-152020-01-152020-01-152019-12-0110.1126/sciadv.aay1357https://infoscience.epfl.ch/handle/20.500.14299/164607WOS:000505069600070Although a clinical breakthrough for cancer treatment, it remains that a minority of patients respond to checkpoint inhibitor (CPI) immunotherapy. The composition of tumor-infiltrating immune cells has been identified as a key factor influencing CPI therapy success. Thus, enhancing tumor immune cell infiltration is a critical challenge. A lack of the chemokine CCL4 within the tumor microenvironment leads to the absence of CD103(+) dendritic cells (DCs), a crucial cell population influencing CPI responsiveness. Here, we use a tumor stroma-targeting approach to deliver CCL4; by generating a fusion protein of CCL4 and the collagen-binding domain (CBD) of von Willebrand factor, we show that CBD fusion enhances CCL4 tumor localization. Intravenous CBD-CCL4 administration recruits CD103(+) DCs and CD8(+) T cells and improves the antitumor effect of CPI immunotherapy in multiple tumor models, including poor responders to CPI. Thus, CBD-CCL4 holds clinical translational potential by enhancing efficacy of CPI immunotherapy.Multidisciplinary SciencesScience & Technology - Other Topicsresistancepd-l1microenvironmenttraffickingmechanismsimmunitysubsetsccr5text::journal::journal article::research article