Alarmin-painted exosomes elicit persistent antitumor immunity in large established tumors in mice

Nat Commun. 2020 Apr 14;11(1):1790. doi: 10.1038/s41467-020-15569-2.

Abstract

Treating large established tumors is challenging for dendritic cell (DC)-based immunotherapy. DC activation with tumor cell-derived exosomes (TEXs) carrying multiple tumor-associated antigen can enhance tumor recognition. Adding a potent adjuvant, high mobility group nucleosome-binding protein 1 (HMGN1), boosts DCs' ability to activate T cells and improves vaccine efficiency. Here, we demonstrate that TEXs painted with the functional domain of HMGN1 (TEX-N1ND) via an exosomal anchor peptide potentiates DC immunogenicity. TEX-N1ND pulsed DCs (DCTEX-N1ND) elicit long-lasting antitumor immunity and tumor suppression in different syngeneic mouse models with large tumor burdens, most notably large, poorly immunogenic orthotopic hepatocellular carcinoma (HCC). DCTEX-N1ND show increased homing to lymphoid tissues and contribute to augmented memory T cells. Importantly, N1ND-painted serum exosomes from cancer patients also promote DC activation. Our study demonstrates the potency of TEX-N1ND to strengthen DC immunogenicity and to suppress large established tumors, and thus provides an avenue to improve DC-based immunotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alarmins / metabolism*
  • Animals
  • Carcinoma, Hepatocellular / immunology*
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / therapy
  • Cell Line
  • Exosomes / metabolism*
  • HMGN1 Protein / genetics
  • HMGN1 Protein / metabolism*
  • HeLa Cells
  • Humans
  • Immunohistochemistry
  • Immunotherapy
  • Liver Neoplasms / immunology*
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / therapy
  • Mice
  • Mice, Inbred C57BL
  • Mice, Nude
  • T-Lymphocytes / metabolism

Substances

  • Alarmins
  • HMGN1 Protein