Your browser doesn't support javascript.
loading
Arsenic trioxide augments immunogenic cell death and induces cGAS-STING-IFN pathway activation in hepatocellular carcinoma.
Li, Xin; Pan, Yu-Fei; Chen, Yi-Bin; Wan, Qian-Qian; Lin, Yun-Kai; Shang, Tai-Yu; Xu, Meng-You; Jiang, Tian-Yi; Pei, Meng-Miao; Tan, Ye-Xiong; Dong, Li-Wei; Wan, Xu-Ying.
Afiliación
  • Li X; Department of Integrated Chinese and Western Medicine, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China.
  • Pan YF; National Center for Liver Cancer, Naval Medical University, Shanghai, China.
  • Chen YB; National Center for Liver Cancer, Naval Medical University, Shanghai, China.
  • Wan QQ; Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China.
  • Lin YK; Department of Integrated Chinese and Western Medicine, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China.
  • Shang TY; National Center for Liver Cancer, Naval Medical University, Shanghai, China.
  • Xu MY; National Center for Liver Cancer, Naval Medical University, Shanghai, China.
  • Jiang TY; School of Life Sciences, Fudan University, Shanghai, China.
  • Pei MM; National Center for Liver Cancer, Naval Medical University, Shanghai, China.
  • Tan YX; Peking University Cancer Hospital, Beijing, China.
  • Dong LW; National Center for Liver Cancer, Naval Medical University, Shanghai, China.
  • Wan XY; Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China.
Cell Death Dis ; 15(4): 300, 2024 Apr 29.
Article en En | MEDLINE | ID: mdl-38684648
ABSTRACT
The treatment of hepatocellular carcinoma (HCC) is particularly challenging due to the inherent tumoral heterogeneity and easy resistance towards chemotherapy and immunotherapy. Arsenic trioxide (ATO) has emerged as a cytotoxic agent effective for treating solid tumors, including advanced HCC. However, its effectiveness in HCC treatment remains limited, and the underlying mechanisms are still uncertain. Therefore, this study aimed to characterize the effects and mechanisms of ATO in HCC. By evaluating the susceptibilities of human and murine HCC cell lines to ATO treatment, we discovered that HCC cells exhibited a range of sensitivity to ATO treatment, highlighting their inherent heterogeneity. A gene signature comprising 265 genes was identified to distinguish ATO-sensitive from ATO-insensitive cells. According to this signature, HCC patients have also been classified and exhibited differential features of ATO response. Our results showed that ATO treatment induced reactive oxygen species (ROS) accumulation and the activation of multiple cell death modalities, including necroptosis and ferroptosis, in ATO-sensitive HCC cells. Meanwhile, elevated tumoral immunogenicity was also observed in ATO-sensitive HCC cells. Similar effects were not observed in ATO-insensitive cells. We reported that ATO treatment induced mitochondrial injury and mtDNA release into the cytoplasm in ATO-sensitive HCC tumors. This subsequently activated the cGAS-STING-IFN axis, facilitating CD8+ T cell infiltration and activation. However, we found that the IFN pathway also induced tumoral PD-L1 expression, potentially antagonizing ATO-mediated immune attack. Additional anti-PD1 therapy promoted the anti-tumor response of ATO in ATO-sensitive HCC tumors. In summary, our data indicate that heterogeneous ATO responses exist in HCC tumors, and ATO treatment significantly induces immunogenic cell death (ICD) and activates the tumor-derived mtDNA-STING-IFN axis. These findings may offer a new perspective on the clinical treatment of HCC and warrant further study.
Asunto(s)
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Carcinoma Hepatocelular / Trióxido de Arsénico / Muerte Celular Inmunogénica / Neoplasias Hepáticas / Proteínas de la Membrana / Nucleotidiltransferasas Límite: Animals / Humans Idioma: En Revista: Cell Death Dis Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Carcinoma Hepatocelular / Trióxido de Arsénico / Muerte Celular Inmunogénica / Neoplasias Hepáticas / Proteínas de la Membrana / Nucleotidiltransferasas Límite: Animals / Humans Idioma: En Revista: Cell Death Dis Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido