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

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.

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.

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.

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.