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Published on: June 12, 2021
AIF1 Regulates the Progression of Esophageal Squamous Cell Carcinoma Through Negative Regulation of Immune T Cell
Xiao Lyu1, Yinping Sun1, Jifeng Zhang2
1Department of Medical Oncology, Zibo Central Hospital, Zibo, 255036, China.
Background:
Esophageal cancer stands as one of the most aggressive and lethal malignancies among digestive tract tumors.
Aims:
This study aimed to explore whether AIF1 regulated immune infiltration in esophageal cancer and its association with TIGIT.
Methods:
AKR cells transfected with an AIF1 overexpression vector were subcutaneously injected into mice. Additionally, mice were treated with a TIGIT monoclonal antibody. Tumor growth was monitored, and the proportions of different T cell subsets in tumor tissues were detected. AKR cells transfected with AIF1 and Treg cells transfected with TIGIT were co-cultured. Cell viability was assessed using the CCK-8 assay. The expression levels of immune infiltration-related markers (FOXP3, TIM3, and IL-6) were detected by ELISA or Western blotting.
Results:
Overexpression of AIF1 combined with TIGIT mAb treatment inhibited tumor growth. This combination promoted the expression of CD3⁺ and IFN-γ (markers of effector T cells) and suppressed the expression of FOXP3 and TIM3 (markers related to immune suppression). In the AIF/TIGIT-treated group, the expressions of pro-inflammatory cytokines (IFN-γ, IL-6, and TNF-α) were up-regulated, while the expressions of anti-inflammatory cytokines (TNF-β and IL-10) were down-regulated. AIF/TIGIT treatment significantly inhibited the expression of immune-specific factors PD-1, FOXP3 in the tissue cells. When TIGIT-overexpressing T cells were co-cultured with cancer cells, cell viability was lower compared to the group with AIF1 overexpression alone. Notably, the group with both AIF1 overexpression and TIGIT overexpression exhibited the lowest cell viability. Under conditions of AIF1 overexpression and TIGIT overexpression, the levels of LDH, TNF-α, and IFN-γ in cancer cells were also the lowest, indicating a synergistic effect on modulating cell function and cytokine secretion.
Conclusions:
AIF1 may regulate the progression of esophageal squamous cell carcinoma by negatively modulating the efflux function of immune T cells via the TIGIT signaling pathway.
Insights
AIF1 and TIGIT monoclonal antibody treatment inhibited esophageal cancer growth by enhancing effector T cell function and suppressing immune suppression markers. This combination therapy shows promise for treating this aggressive malignancy.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Esophageal cancer is a highly lethal malignancy.
- Understanding immune regulation in esophageal cancer is crucial for developing effective therapies.
Purpose of the Study:
- To investigate the role of AIF1 in regulating immune infiltration in esophageal cancer.
- To explore the association between AIF1 and TIGIT in esophageal cancer progression.
Main Methods:
- In vivo studies using AIF1-overexpressing AKR cells and TIGIT monoclonal antibody treatment in mice.
- In vitro co-culture experiments with AIF1-overexpressing cancer cells and TIGIT-overexpressing T cells.
- Assessment of tumor growth, T cell subset proportions, cell viability (CCK-8 assay), and immune marker expression (ELISA, Western blotting).
Main Results:
- Combined AIF1 overexpression and TIGIT mAb treatment significantly inhibited tumor growth.
- This combination therapy promoted effector T cell markers (CD3+, IFN-γ) and suppressed immune suppressive markers (FOXP3, TIM3).
- Synergistic effects were observed, leading to reduced cancer cell viability and modulated cytokine secretion.
Conclusions:
- AIF1 negatively modulates immune T cell function via the TIGIT signaling pathway in esophageal squamous cell carcinoma.
- Targeting AIF1 and TIGIT may represent a novel therapeutic strategy for esophageal cancer.
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