A hepatitis b virus-derived peptide exerts an anticancer effect via TNF/iNOS-producing dendritic cells in tumor-bearing mouse model

Soo Bin Yang, Mi Hyun Lee, Bo Ram Kim, Yu Min Choi, Bum Joon Kim

Research output: Contribution to journalArticlepeer-review

Abstract

Recently, we reported a 6-mer hepatitis B virus (HBV)-derived peptide, Poly6, that exerts antiviral effects against human immunodeficiency virus type 1 (HIV-1). Here, we explored the immunotherapeutic potential of Poly6 via its administration into dendritic cells (DCs) in a mouse model. Our data revealed that Poly6 treatment led to enhanced production of tumor necrosis factor alpha (TNF-α) and inducible nitric oxide synthase (iNOS)-producing DCs (Tip-DCs) in a type 1 interferon (IFN-I)-dependent manner via the induction of mitochondrial stress. Poly6 treatment in mice implanted with MC38 cells, a murine colon adenocarcinoma line, led to attenuated tumor formation, primarily due to direct cell death induced by Tip-DC mediated nitric oxide (NO) production and indirect killing by Tip-DC mediated cluster of differentiation 8 (CD8) cytotoxic T lymphocyte (CTL) activation via CD40 activation. Moreover, Poly6 treatment demonstrated an enhanced anticancer effect with one of the checkpoint inhibitors, the anti PD-L1 antibody. In conclusion, our data reveal that Poly6 treatment elicits an antitumor immune response in mice, possibly through NO-mediated oncolytic activity via Tip-DC activation and Tip-DC mediated CTL activation. This suggests that Poly6 represents a potential adjuvant for cancer immunotherapy by enhancing the anticancer effects of immune checkpoint inhibitors.

Original languageEnglish
Article number407
Pages (from-to)1-17
Number of pages17
JournalCancers
Volume13
Issue number3
DOIs
StatePublished - 1 Feb 2021

Keywords

  • CD40
  • Cancer immunotherapy
  • HBV-derived poly6 peptide
  • TNF/iNOS-producing DCs (Tip-DCs)
  • Type 1 interferon (IFN-I)

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