Department of Bioengineering, University of California, Los Angeles, California, 90095, USA.
Earle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical Center, Portland, Oregon, 97213, USA.
Adv Sci (Weinh). 2023 Feb;10(5):e2206001. doi: 10.1002/advs.202206001. Epub 2022 Dec 16.
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.
肿瘤相关脂肪细胞（TAAs）招募单核细胞，并促进其分化为支持肿瘤发展的肿瘤相关巨噬细胞（TAMs）。在这里，TAAs 被设计为促进 TAMs 向肿瘤抑制性 M1 表型极化。Telratolimod 是一种 Toll 样受体 7/8 激动剂，被装载到脂肪细胞的脂滴中，在肿瘤细胞触发脂肪分解时在肿瘤部位释放。局部给予负载药物的脂肪细胞增加了原发性和远处肿瘤中的肿瘤抑制性 M1 巨噬细胞，并抑制了黑色素瘤模型中的肿瘤生长。此外，负载药物的脂肪细胞改善了肿瘤微环境中 CD8 T 细胞介导的免疫反应，并有利于肿瘤引流淋巴结中树突状细胞的成熟。
