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

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.

Multifunctional polysaccharide composited microneedle for oral ulcers healing

“…This is consistent with the findings of previous cell experiments. Following tissue injury, M1 macrophages secrete pro-inflammatory cytokines such as TNF-α, IL-1, IL-6, and IL-12, which have anti-proliferative functions [ 39 ]. While M2 anti-inflammatory macrophages can improve immunomodulation, tissue repair.…”

Primary adipocytes as targetable drug depot to prevent post-surgical cancer recurrence

“…Due to its low immunogenicity and association with various diseases, adipocyte is an attractive engineering target for drug delivery applications. However, existing adipocyte engineering methodologies have been largely limited to the physical adsorption of cargos [ 15 , 39 ]. For instance, loading of anticancer drugs into adipocytes was attempted via simple mixing.…”

Stromal cells in the tumor microenvironment: accomplices of tumor progression?

“…In addition, adipocytes can also support tumor progression by regulating immune cells in TME, such as the levels of exosome microRNA (miRNA)-155 increased during co-culture of tumor cells and adipocytes, thereby recruiting macrophages and promoting their differentiation into TAMs that support tumor development [ 220 – 222 ] In addition, visfatin secreted by CAAs can also induce M2 macrophage polarization and accelerate the glycolysis process in malignant tumor cells [ 223 ]. Not only that adipocytes can also acquire myofibroblast and macrophage-like features through metabolic reprogramming and dedifferentiation (that is “adipocytes-stromal switch”) thereby promoting tumor progression [ 224 ].…”