Tissue & cell · 2026
Ablation of ASF1B mitigates the proliferation of A549 cells and enhances anti-PD-L1 therapy by regulating ferroptosis.
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Shi Jiamin, Fang Ying, Hu Shuyi, Zhu Yifei, Hu Qin, Liu Ying, Wang Xiaohua, Zhou Guoren
Аннотация
BACKGROUND: Non-small cell lung cancer (NSCLC) ranks among the most prevalent malignant neoplasms globally. Anti-silencing function 1B (ASF1B) has been reported to be highly expressed in NSCLC and promotes oncogenesis; however, the excise role of ASF1B underlying the immunotherapy of NSCLC remains unclear.
METHODS: The expression level of ASF1B in NSCLC tissues and cell lines was examined using bioinformatic analysis, immunohistochemistry, quantitative real-time PCR and western blot. Cell counting kit-8 and EdU assays were performed to asses cell proliferation. Iron accumulation and lipid peroxidation were measured using their commercial kits. The co-culture assay was conducted with A549 cells and human peripheral blood mononuclear cells (PBMC) to stimulate the immune microenvironment in vitro. Flow cytometry analysis was used to detect the apoptosis of CD8+ T cells, and the production of interleukin (IL)-2 and interferon (IFN)-γ was examined by ELISA. Moreover, A549 cells were treated with Ferrostatin-1 (Fer-1) or Pifithrin-α (PFT-α), a p53 inhibitor, to conduct the rescue assay. Mouse Lewis lung carcinoma cells were subcutaneously injected into C57BL/6 mice to establish the in vivo tumorigenesis model and the tumor growth was monitored.
RESULTS: ASF1B was upregulated in NSCLC tumors and positively correlated with PD-L1. ASF1B knockdown significantly reduced cell viability and the EdU-positive cells. Meanwhile, ASF1B knockdown promoted ferroptosis of A549 cells through increasing accumulation of iron and lipid peroxidation and regulating ferroptosis-related proteins. Also, ASF1B deficiency reduced the apoptosis of CD8+ T cells, boosted the release of IL-2 and IFN-γ, and reduced the expression of PD-L1/PD-1 in PBMCs. The above changes were partly abolished by additional treatment by Fer-1 or PFT-α. Furthermore, ASF1B deficiency restricted the tumor growth and enhanced the anti-tumor activity of anti-PD-L1 in vivo.
CONCLUSION: Collectively, these findings suggest that ASF1B deficiency exerts anti-tumor effects and anti-tumor immunity by regulating p53-related ferroptosis.
METHODS: The expression level of ASF1B in NSCLC tissues and cell lines was examined using bioinformatic analysis, immunohistochemistry, quantitative real-time PCR and western blot. Cell counting kit-8 and EdU assays were performed to asses cell proliferation. Iron accumulation and lipid peroxidation were measured using their commercial kits. The co-culture assay was conducted with A549 cells and human peripheral blood mononuclear cells (PBMC) to stimulate the immune microenvironment in vitro. Flow cytometry analysis was used to detect the apoptosis of CD8+ T cells, and the production of interleukin (IL)-2 and interferon (IFN)-γ was examined by ELISA. Moreover, A549 cells were treated with Ferrostatin-1 (Fer-1) or Pifithrin-α (PFT-α), a p53 inhibitor, to conduct the rescue assay. Mouse Lewis lung carcinoma cells were subcutaneously injected into C57BL/6 mice to establish the in vivo tumorigenesis model and the tumor growth was monitored.
RESULTS: ASF1B was upregulated in NSCLC tumors and positively correlated with PD-L1. ASF1B knockdown significantly reduced cell viability and the EdU-positive cells. Meanwhile, ASF1B knockdown promoted ferroptosis of A549 cells through increasing accumulation of iron and lipid peroxidation and regulating ferroptosis-related proteins. Also, ASF1B deficiency reduced the apoptosis of CD8+ T cells, boosted the release of IL-2 and IFN-γ, and reduced the expression of PD-L1/PD-1 in PBMCs. The above changes were partly abolished by additional treatment by Fer-1 or PFT-α. Furthermore, ASF1B deficiency restricted the tumor growth and enhanced the anti-tumor activity of anti-PD-L1 in vivo.
CONCLUSION: Collectively, these findings suggest that ASF1B deficiency exerts anti-tumor effects and anti-tumor immunity by regulating p53-related ferroptosis.