Adipocytes Encapsulating Telratolimod Recruit and Polarize Tumor-Associated Macrophages for Cancer Immunotherapy.
Adv Sci (Weinh)
oregon; eacri; chiles
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.
Earle A. Chiles Research Institute
Wen, Di; Liang, Tingxizi; Chen, Guojun; Li, Hongjun; Wang, Zejun; Wang, Jinqiang; Fu, Ruxing; Han, Xiao; Ci, Tianyuan; Zhang, Yuqi; Abdou, Peter; Li, Ruoxin; Bu, Linlin; Dotti, Gianpietro; and Gu, Zhen, "Adipocytes Encapsulating Telratolimod Recruit and Polarize Tumor-Associated Macrophages for Cancer Immunotherapy." (2022). Articles, Abstracts, and Reports. 6820.