Latexin (LXN) enhances tumor immune surveillance in mice by inhibiting Treg cells through the macrophage exosome pathway.

Abstract

Latexin (LXN) is a secreted protein with a molecular weight of 29 KD, which is considered a tumor suppressor and plays an important role in the inflammatory immune response. LXN is highly expressed in macrophages and regulates macrophage polarity and tumor immune escape, demonstrating excellent clinical potential. However, its mechanism is still unclear. In this study, a macrophage-T cell co-culture system is established to clarify the secretion of macrophage LXN into the extracellular through exosomes. The results indicate that LXN in macrophage-derived exosomes is functional, that is, LXN-enriched exosome inhibits CD4⁺T cell differentiation into Treg cells in vitro and in vivo, and exhibits good tumor suppressive effects. Based on this discovery, a biomimetic nanoparticle loaded with LXN protein (MØ@LXN-NPS) is designed and synthesized. Furthermore, the MØ@LXN-NPS shows excellent performance in both in vivo and in vitro, especially in enhancing tumor immune surveillance by inhibiting Treg cells in tumor microenvironment, thus exhibiting excellent anti-tumor activity. This study provides a demonstration for the transition of biomolecules from functional research to engineering applications. The excellent performance of MØ@LXN-NPS in tumor immune regulation suggests that the engineered biomimetic nanomedicine has good clinical application prospects.