Adipocytes Encapsulating Telratolimod Recruit and Polarize Tumor‐Associated Macrophages for Cancer Immunotherapy. Issue 5 (16th December 2022)

• Record Type: Journal Article
• Authors: 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; Gu, Zhen
• Is Part Of: Advanced science. Volume 10:Issue 5(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-12-16
• Subjects: adipocyte -- cancer immunotherapy -- drug delivery -- macrophage; Science -- Periodicals; 505
• DOI: 10.1002/advs.202206001
• Languages: English
• ISSNs: 2198-3844

Abstract

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. Abstract : The adipocytes are engineered to recruit macrophages and further deliver the lipid conjugated toll‐like receptor 7/8 agonist, which polarized the tumor‐associated macrophages to the M1 phenotype for cancer immunotherapy. By leveraging the tumor cell‐triggered lipolysis, a tumor‐responsive drug release is achieved and the systemic antitumor immune response suppressed both primary and distant tumor growth.