Autophagy enhances antitumor immune responses induced by irradiated hepatocellular carcinoma cells engineered to express hepatitis B virus X protein

Yan,Yingying; Liu,Ning; Lu,Lian; Zang,Chuan-Mou; Shao,Bin; Li,Yuhua; Wen,Yanjun; Wei,Yuquan; Cheng,Ping

doi:10.3892/or.2013.2531

Autophagy enhances antitumor immune responses induced by irradiated hepatocellular carcinoma cells engineered to express hepatitis B virus X protein

Authors:
- Yingying Yan
- Ning Liu
- Lian Lu
- Chuan-Mou Zang
- Bin Shao
- Yuhua Li
- Yanjun Wen
- Yuquan Wei
- Ping Cheng
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Affiliations: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, P.R. China
Published online on: June 10, 2013 https://doi.org/10.3892/or.2013.2531
Pages: 993-999

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Abstract

Hepatitis B virus X protein (HBx) plays a critical role in malignancy transformation of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). HBx sequence has been mapped with multi-epitopes which can elicit robust specific cytolytic T lymphocyte (CTL) responses. In our previous study, we developed an adenoviral vaccine against HBx oncoproteins to prevent growth of HBV-associated HCC. However, due to the weak immunogenicity of tumor antigen and pre-existing virus-neutralizing antibodies to the vaccine carrier preventing the vector from transducing target cells, the development of novel methods to enhance antigen presentation is urgently required. In the present study, we developed an adenoviral‑mediated genetic engineering of hepatoma cell vaccine to express HBx and to evaluate if the novel vaccine could elicit specific immune responses. Our data showed that the irradiated tumor cells engineered to express HBx could significantly induce antitumor immune responses in vivo. The novel vaccine could induce a specific CTL response to recognize and lyse HBx-positive hepatoma cells in vitro. Both CD8+ T and CD4+ T lymphocytes are involved in the antitumor immune response induced by the novel vaccine. Furthermore, numerous autophagosomes and autolysosomes were found in the irradiated tumor cells engineered to express HBx. The results demonstrated that the irradiated HBx-modified tumor cell vaccine was a potent and promising therapeutic agent against HBx-positive HCC via induction of autophagy-enhanced CD8+ T and CD4+ T lymphocyte-mediated antitumor immune responses. The present findings have implications for the development of clinical immunotherapy against HBV-associated HCC.

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