Adipocytes Encapsulating Telratolimod Recruit and Polarize Tumor-Associated Macrophages for Cancer Immunotherapy
Di Wen 1 2, Tingxizi Liang 1 3, Guojun Chen 1, Hongjun Li 1 3, Zejun Wang 1, Jinqiang Wang 1 3, Ruxing Fu 1, Xiao Han 1, Tianyuan Ci 1, Yuqi Zhang 1 3, Peter Abdou 1, Ruoxin Li 1, Linlin Bu 1, Gianpietro Dotti 4, Zhen Gu 1 3 5 6
Tumor-connected adipocytes (TAAs) recruit monocytes and promote their differentiation into tumor-connected macrophages (TAMs) that support tumor development. Here, TAAs are engineered to advertise the polarization of TAMs towards the tumor suppressive M1 phenotype. Telratolimod, a toll-like receptor 7/8 agonist, is loaded in to the fat tiny droplets of adipocytes to be sold in the tumor site upon tumor cell-triggered lipolysis. In your area administered drug-loaded adipocytes elevated tumor suppressive M1 macrophages both in primary and distant tumors and covered up tumor development in a melanoma model. In addition, drug-loaded adipocytes improved CD8 T cell-mediated immune responses inside the tumor microenvironment and favored dendritic cell maturation within the tumor draining lymph nodes.