1. Adipocytes Encapsulating Telratolimod Recruit and Polarize Tumor‐Associated Macrophages for Cancer Immunotherapy
- Author
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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
- Subjects
Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Immunology ,Cancer ,Humans ,Tumor-Associated Macrophages ,Macrophages ,Immunotherapy ,Melanoma ,Adipocytes ,Tumor Microenvironment ,adipocyte ,cancer immunotherapy ,drug delivery ,macrophage - 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.
- Published
- 2023