학술논문

Adipocytes Encapsulating Telratolimod Recruit and Polarize Tumor‐Associated Macrophages for Cancer Immunotherapy
Document Type
article
Source
Advanced Science. 10(5)
Subject
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
Language
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.