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Published on: May 24, 2024
Arsenic trioxide is an immune adjuvant in liver cancer treatment
Lei Wang1, Ren Wang2, Lin Fan2
1Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Disease of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan 430071, Hubei, PR China.
Abstract:
Tumor cells are inhibited effectively by As2O3in vitro and in vivo, although the underlying immune regulatory mechanisms remain unknown. Regulatory T cells play a key role in tumor immune escape. In the present study, we aimed to assess the in vivo effects of As2O3 on the immune status in hepatic cancer and its in vitro regulatory role in cytokine-induced killers(CIKs)cytotoxicity. In a tumor H22 xenograft model of hepatic cancer, we demonstrated that As2O3 treatment decreased tumor volumes and weights, and improved survival by reducing Tregs infiltration into the tumor. Moreover, our data indicated that the exact immune regulatory mechanism of As2O3 might involve elevated CD3+T lymphocyte amounts more than reduced Tregs levels. Furthermore, As2O3 significantly improved CIKs cytotoxicity in vitro by decreasing CD4+T lymphocytes and Tregs, and increasing CD8+T lymphocytes. Our results suggested that As2O3 might act as an immune adjuvant in liver carcinoma treatment by increasing T lymphocytes and decreasing Treg infiltrated into the tumor.
Insights
Arsenic trioxide (As2O3) effectively inhibits liver cancer by reducing regulatory T cells (Tregs) and boosting T lymphocytes. This immune modulation enhances anti-tumor responses and improves survival in hepatic cancer models.
Area of Science:
- Immunology
- Oncology
- Pharmacology
Background:
- Tumor cells are effectively inhibited by arsenic trioxide (As2O3) in vitro and in vivo.
- The precise immune regulatory mechanisms underlying As2O3's anti-tumor effects are not fully understood.
- Regulatory T cells (Tregs) are known to play a critical role in tumor immune escape.
Purpose of the Study:
- To investigate the in vivo effects of As2O3 on the immune status in hepatic cancer.
- To assess the in vitro regulatory role of As2O3 in cytokine-induced killer (CIK) cell cytotoxicity.
Main Methods:
- Utilized a H22 xenograft model of hepatic cancer in vivo.
- Administered As2O3 treatment to assess effects on tumor volume, weight, survival, and immune cell infiltration (Tregs, CD3+ T lymphocytes).
- Evaluated As2O3's in vitro effects on CIK cell cytotoxicity, CD4+ T lymphocytes, CD8+ T lymphocytes, and Tregs.
Main Results:
- As2O3 treatment significantly decreased tumor volumes and weights, and improved survival in the hepatic cancer model.
- As2O3 reduced Treg infiltration into the tumor and increased CD3+ T lymphocyte amounts.
- In vitro, As2O3 enhanced CIK cell cytotoxicity by decreasing CD4+ T lymphocytes and Tregs, while increasing CD8+ T lymphocytes.
Conclusions:
- As2O3 demonstrates potential as an immune adjuvant in liver carcinoma treatment.
- As2O3 enhances anti-tumor immunity by modulating T lymphocyte populations and reducing Treg infiltration.
- The findings suggest As2O3 could be a valuable therapeutic agent for hepatic cancer by boosting the host's immune response.
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