BATF-Activated AIM2 Mediates Immune Escape in Lung Adenocarcinoma by Regulating PD-L1.

Abstract

Introduction: Immunotherapy has demonstrated encouraging outcomes in tackling lung adenocarcinoma (LUAD), but immune escape may bring negative impacts. Only a single study has demonstrated the function of AIM2 in LUAD and reported that NF-κB and STAT1 are the chief transcription factors, this study is designed to analyze the role of AIM2 and examine the transcription factor, BATF in LUAD immunotherapy.

Methods: Bioinformatics methods to analyze the expression and binding sites of AIM2 and BATF in LUAD, as well as the correlation between AIM2 and PD-L1. Dual-luciferase and chromatin immunoprecipitation assays were used to verify the binding of AIM2 and BATF. qRT-PCR and Western blot assayed expression of AIM2, BATF, and PD-L1 in LUAD. MTT measured cell viability, flow cytometry detected cell apoptosis, cytotoxicity assays measured the toxicity of CD8+ T cells to cancer cells, and enzyme-linked immunosorbent assay measured the expression of related cytokines. Immunohistochemistry detected the protein expression levels of AIM2, BATF, PD-L1, and CD8 in tumor tissue.

Results: AIM2 and BATF were both highly expressed in LUAD, and there was a targeted binding relationship. BATF promoted LUAD cell proliferation and inhibited apoptosis by affecting AIM2 expression. The downregulation of AIM2 and PD-L1 expression inhibited PD-L1 and activated CD8+ T cells. The rescue experiment manifested that increased BATF weakened repression of AIM2 silencing on LUAD tumor immune escape in vitro and in vivo.

Conclusion: BATF promoted AIM2 expression, upregulated PD-L1, inhibited CD8+ T cell activity, and ultimately led to immune escape in LUAD. Our research uncovered an innovative outlook on the intricate regulation of immune checkpoint molecules and proposed a new approach to target the BATF/AIM2 axis in tumor immunotherapy.