d -lactate modulates M2 tumor-associated macrophages and remodels immunosuppressive tumor microenvironment for hepatocellular carcinoma

The polarization of tumor-associated macrophages (TAMs) from M2 to M1 phenotype demonstrates great potential for remodeling the immunosuppressive tumor microenvironment (TME) of hepatocellular carcinoma (HCC). d -lactate (DL; a gut microbiome metabolite) acts as an endogenous immunomodulatory agent that enhances Kupffer cells for clearance of pathogens. In this study, the potential of DL for transformation of M2 TAMs to M1 was confirmed, and the mechanisms underlying such polarization were mainly due to the modulation of phosphatidylinositol 3-kinase/protein kinase B pathway. A poly(lactide- co -glycolide) nanoparticle (NP) was used to load DL, and the DL-loaded NP was modified with HCC membrane and M2…

• NN
  National Natural Science Foundation of China

  Awards: 81774240, 82222074, 82074154
• PG
  People's Government of Jilin Province
• JU
  Jilin University

  Award: 2022JBGS05
• SU
  Shanghai University of Traditional Chinese Medicine

  Award: 81774240
• UO
  University of North Carolina at Chapel Hill