Statin in combination with cisplatin makes favorable tumor-immune microenvironment for immunotherapy of head and neck squamous cell carcinoma

Minsu Kwon, Gi Hoon Nam, Hanul Jung, Seong A. Kim, Seohyun Kim, Yeonju Choi, Yoon Se Lee, Hyo Jung Cho, In San Kim

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

The purpose of this study was to determine whether statins can enhance anticancer effects in head and neck squamous cell carcinoma (HNSCC) when used with cisplatin and act as immunogenic cell death (ICD) inducers that can be used in cancer immunotherapy. Statins alone showed both in vitro and in vivo inhibitory effects against HNSCC, and synergistic antitumor effects were observed when combined with cisplatin in a syngeneic murine HNSCC model. Statins increased calreticulin exposure and endoplasmic reticulum stress-related signals in HNSCC cells. In addition, it was confirmed that statins could activate antigen-presenting cells and tumor-specific CD8+ T cells with an increase in their numbers in the tumor tissues and draining lymph nodes, with this effect showing significant improvement following the combination therapy with cisplatin. Moreover, in triple combination with both cisplatin and anti-programmed cell death 1 receptor (anti-PD-1) antibody, statins dramatically induced further tumor eradication and improved the survival of tumor-bearing mice. Taken together, these results demonstrate that statins, administered in combination with anti-PD-1 antibody, could enhance the anticancer effect of cisplatin and potentiate the efficacy of immunotherapy for HNSCC and present a rationale for repurposing statins as an adjuvant immunotherapeutic option for HNSCC.

Original languageEnglish
Pages (from-to)198-210
Number of pages13
JournalCancer letters
Volume522
DOIs
Publication statusPublished - 2021 Dec 1

Keywords

  • Anticancer drug combinations
  • Cis-diamminedichloroplatinum (II)
  • Head and neck neoplasms
  • Hydroxymethylglutaryl-CoA reductase inhibitors
  • Immunogenic cell death

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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