Kwon, Minsu Nam, Gi-Hoon Jung, Hanul Kim, Seong A. Kim, Seohyun Choi, Yeonju Lee, Yoon Se Cho, Hyo Jung Kim, In-San 2024-01-19T13:03:14Z 2024-01-19T13:03:14Z 2022-01-10 2021-12-01 0304-3835 https://pubs.kist.re.kr/handle/201004/115944 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. English ELSEVIER IRELAND LTD DOUBLE-BLIND ANTITUMOR IMMUNITY MEVALONATE PATHWAY PHASE-III CANCER DEATH SIMVASTATIN CHEMOTHERAPY MULTICENTER PROGRESSION Statin in combination with cisplatin makes favorable tumor-immune microenvironment for immunotherapy of head and neck squamous cell carcinoma Article 10.1016/j.canlet.2021.09.029 1 CANCER LETTERS, v.522, pp.198 - 210 CANCER LETTERS 522 198 210 scie scopus 000703906900003 2-s2.0-85115922084 Oncology Oncology Article DOUBLE-BLIND ANTITUMOR IMMUNITY MEVALONATE PATHWAY PHASE-III CANCER DEATH SIMVASTATIN CHEMOTHERAPY MULTICENTER PROGRESSION Anticancer drug combinations Cis-diamminedichloroplatinum (II) Head and neck neoplasms Immunogenic cell death Hydroxymethylglutaryl-CoA reductase inhibitors