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

Publication Title

Adv Sci (Weinh)

Document Type

Article

Publication Date

12-16-2022

Keywords

oregon; eacri; chiles

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.

Clinical Institute

Cancer

Specialty/Research Institute

Oncology

Specialty/Research Institute

Earle A. Chiles Research Institute

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