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

  • Adv Sci (Weinh). 2022 Dec 16;e2206001. doi: 10.1002/advs.202206001.
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
Affiliations
  • 1. Department of Bioengineering, University of California, Los Angeles, California, 90095, USA.
  • 2. Earle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical Center, Portland, Oregon, 97213, USA.
  • 3. Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
  • 4. Department of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
  • 5. Jinhua Institute of Zhejiang University, Jinhua, 321299, P. R. China.
  • 6. Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, China.
PMID: 36526596 DOI: 10.1002/advs.202206001
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.

Keywords
adipocyte; cancer immunotherapy; drug delivery; macrophage.
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