Adipocytes Encapsulating Telratolimod Recruit and Polarize Tumor-Associated Macrophages for Cancer Immunotherapy

Abstract

Tumor-associated adipocytes (TAAs) recruit monocytes and promote their differentiation into tumor-associated macrophages (TAMs) that support tumor development. Here, TAAs are engineered to promote the polarization of TAMs to the tumor suppressive M1 phenotype. Telratolimod, a toll-like receptor 7/8 agonist, is loaded into the lipid droplets of adipocytes to be released at the tumor site upon tumor cell-triggered lipolysis. Locally administered drug-loaded adipocytes increased tumor suppressive M1 macrophages in both primary and distant tumors and suppressed tumor growth in a melanoma model. Furthermore, drug-loaded adipocytes improved CD8⁺ T cell-mediated immune responses within the tumor microenvironment and favored dendritic cell maturation in the tumor draining lymph nodes.

Keywords: adipocyte; cancer immunotherapy; drug delivery; macrophage.