2. Academic Validation
  3. Adipocytes Encapsulating Telratolimod Recruit and Polarize Tumor-Associated Macrophages for Cancer Immunotherapy

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

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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