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

Abstract

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.

• Authors: Zhaoting Li, Yingyue Ding, Jun Liu, Jianxin Wang, Fanyi Mo, Yixin Wang, Ting-Jing Chen-Mayfield, Paul M Sondel, Seungpyo Hong, Quanyin Hu
• Journal: Nature communications (Nat Commun) Vol. 13 Issue 1 Pg. 1845 (04 06 2022) ISSN: 2041-1723 [Electronic] England
• PMID: 35387972 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural)
• Copyright: © 2022. The Author(s).

Chemical References

• Hydrogels

Topics

• Blood Platelets
• Cell-Derived Microparticles
• Humans
• Hydrogels
• Immunotherapy (methods)
• Neoplasm Recurrence, Local
• Tumor Microenvironment
• Tumor-Associated Macrophages