-activated promotes lung adenocarcinoma progression and inhibits CD4/CD8 T-cell infiltrations by targeting signaling pathway.

Background: Immune-associated genes play vital roles in the tumorigenesis, progression and immunotherapy responses of malignant tumors. This study aimed to comprehensively evaluate the role and mechanism of novel immune-associated gene integrin β4 () in the progression and immune microenvironment of lung adenocarcinoma (LUAD).

Methods: There were 770 immune-associated genes curated from NanoString PanCancer Immune Profiling Panel. Differentially expressed immune-related genes were initially screened using transcriptome data from 57 paired LUAD samples in The Cancer Genome Atlas (TCGA) and 15 paired LUAD samples in GSE31210, and were further validated in 19 paired LUAD samples from our institution. Log-rank test was adopted to identify LUAD prognosis associated genes. Among the identified differentially expressed genes, was ultimately chosen for further analysis. Subsequently, the functionality and mechanisms of were investigated in two LUAD cell lines, A549 and PC9, which exhibited relatively high expression levels of . Following this, the impact of on the proliferation and metastasis of LUAD was evaluated using nude mice. Additionally, its effect on T cell infiltration was studied using immunocompetent C57BL/6J mice.

Results: was found to be significantly up-regulated in LUAD and associated with an unfavorable prognosis. Functionally, could promote LUAD cell proliferation, migration and invasion. Consistently, experiments demonstrated that knockdown suppressed LUAD tumor growth and metastasis. Additionally, could suppress CD4 and CD8 T-cell infiltrations in LUAD cells. Mechanistically, could activate the signaling pathway by interacting with . Furthermore, could directly bind to the promoter and transcriptionally activate in LUAD cells. In addition, , a ligand of , was found to promote LUAD progression by activating the signaling.

Conclusions: was transcriptionally activated by , and could promote LUAD progression and inhibit CD4/CD8 T-cell infiltrations by activating the signaling pathway. may serve as a potential immunotherapeutic target of LUAD.