Depletion of tumor associated macrophages enhances local and systemic platelet-mediated anti-PD-1 delivery for post-surgery tumor recurrence treatment

Zhaoting Li, Yingyue Ding, Jun Liu, Jianxin Wang, Fanyi Mo, Yixin Wang, Ting Jing Chen-Mayfield, Paul M. Sondel, Seungpyo Hong, Quanyin Hu

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30 Citations (Scopus)


Immunosuppressive cells residing in the tumor microenvironment, especially tumor associated macrophages (TAMs), hinder the infiltration and activation of T cells, limiting the anti-cancer outcomes of immune checkpoint blockade. Here, we report a biocompatible alginate-based hydrogel loaded with Pexidartinib (PLX)-encapsulated nanoparticles that gradually release PLX at the tumor site to block colony-stimulating factor 1 receptors (CSF1R) for depleting TAMs. The controlled TAM depletion creates a favorable milieu for facilitating local and systemic delivery of anti-programmed cell death protein 1 (aPD-1) antibody-conjugated platelets to inhibit post-surgery tumor recurrence. The tumor immunosuppressive microenvironment is also reprogrammed by TAM elimination, further promoting the infiltration of T cells into tumor tissues. Moreover, the inflammatory environment after surgery could trigger the activation of platelets to facilitate the release of aPD-1 accompanied with platelet-derived microparticles binding to PD-1 receptors for re-activating T cells. All these results collectively indicate that the immunotherapeutic efficacy against tumor recurrence of both local and systemic administration of aPD-1 antibody-conjugated platelets could be strengthened by local depletion of TAMs through the hydrogel reservoir.

Original languageEnglish
Article number1845
JournalNature communications
Issue number1
Publication statusPublished - 2022 Dec

Bibliographical note

Funding Information:
This work was supported by P30CA014520-UW Carbone Cancer Center Support Grant (CCSG) and the start-up package from the University of Wisconsin-Madison (to Q.H.). S.H. acknowledge the funding support from Wisconsin Center for NanoBioSystems and Milton J. Henrichs Chair fund. We acknowledge the Dr. Glen Kwon’s lab for the help with nanoparticle characterization. We also want to thank optical imaging core, small animal facilities, flow cytometry core and histological core for their help with this study. We acknowledge Dr. Kevin Huang for the help with Cryo SEM imaging.

Publisher Copyright:
© 2022, The Author(s).

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • General
  • Physics and Astronomy(all)


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