BATF2 inhibits PD-L1 expression and regulates CD8+ T-cell infiltration in non-small cell lung cancer
Junwei Liu1, Jie Li2, Zhan Tuo3
1Department of Thoracic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China.
Abstract:
Immune checkpoint blockades have made huge breakthrough among some cancer types including lung cancer. However, only a small proportion of patients will benefit from immune checkpoint blockades; other patients have no or minor response to immunotherapy. The underlying mechanisms and efficient biomarkers to predict immunotherapy resistances remain unclear and lacking. In this study, BATF2 knockout mice, human xenograft mice, were used for in vivo studies. Relevant RNA and protein levels were analyzed by RT-quantitative PCR and Western blotting. As a result, we found that the expression of BATF2 is negatively correlated with expression of programmed death-ligand 1 in the plasma of patients. Mechanically, we showed that BATF2 inhibits programmed death-ligand 1 expression in cancer cells by inhibiting the PI3K-AKT pathway where ZEB2 plays an important role in this process. Based on bioinformatics analysis, we found that the function of BATF2 in promoting antitumor immune response in patients with non-small cell lung cancer, which is mediated by BATF2, enhances CD8+ T-cell infiltration as well as activation. The expression of BATF2 from circulating tumor cells and tissues can be serve as an efficient biomarker to predict diagnosis, prognosis, and immunotherapy efficacy.
Insights
The study found that BATF2 inhibits programmed death-ligand 1, improving immunotherapy response in lung cancer. BATF2 expression can predict diagnosis, prognosis, and treatment efficacy.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Immune checkpoint inhibitors (ICIs) show promise in cancer therapy, but response rates vary significantly.
- Mechanisms of immunotherapy resistance and reliable predictive biomarkers are urgently needed, particularly for lung cancer.
Purpose of the Study:
- To investigate the role of BATF2 in regulating immune checkpoint ligand expression and its impact on antitumor immunity.
- To identify BATF2 as a potential biomarker for predicting immunotherapy efficacy in non-small cell lung cancer (NSCLC).
Main Methods:
- In vivo studies using BATF2 knockout and human xenograft mouse models.
- Analysis of RNA and protein expression via RT-quantitative PCR and Western blotting.
- Bioinformatic analysis of patient data to correlate BATF2 expression with immune responses.
Main Results:
- BATF2 expression is negatively correlated with programmed death-ligand 1 (PD-L1) levels in patient plasma.
- BATF2 suppresses PD-L1 expression by inhibiting the PI3K-AKT pathway, involving ZEB2.
- BATF2 promotes antitumor immunity by enhancing CD8+ T-cell infiltration and activation in NSCLC.
Conclusions:
- BATF2 plays a critical role in modulating the tumor immune microenvironment and overcoming immunotherapy resistance.
- BATF2 expression in circulating tumor cells and tissues serves as a promising biomarker for predicting NSCLC diagnosis, prognosis, and response to immunotherapy.
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