Modulation of the tumor immune microenvironment by Interferon Regulatory Factor 8 enhances immunotherapy in lung adenocarcinoma

Interferon regulatory factors (IRFs) are integral in governing the expression of Type I interferon (IFN) genes. However, the precise role of IRFs in lung adenocarcinoma remains elusive. Our objective is to elucidate the prognostic implications of IRFs and their potential influence on the immunotherapeutic response in patients with lung adenocarcinoma (LUAD). The association between IRFs expression and clinical as well as prognostic features was evaluated utilizing the TCGA database. Prognostic determinants for LUAD were pinpointed via univariate and multivariate analyses. Nomogram to evaluate prognosis predicated on IRF expression levels. Gene enrichments were conducted to elucidate the mechanisms of action. The degree of immune infiltration was using bioinformatics methods and was validated through a single-cell dataset. We compiled our unique cohort of LUAD patients who underwent anti-PD-1 therapy for subsequent immunohistochemistry and multicolor immunofluorescence staining to gauge the conclusion above. Our findings revealed that IRF8 serves as an independent risk factor for overall survival (OS) in patients with LUAD. An analysis of patients undergoing immunotherapy revealed a positive association between the expression of IRF8 and the response to the treatment. In our specific cohort treated with anti-PD-1, high IRF8 expression was observed to enhance immunotherapy response and prolong OS by modulating immune cell infiltration. Our retrospective analysis suggests that elevated IRF8 expression correlates with improved prognosis in LUAD, with higher IRF8 expression being predictive of a more robust immunotherapy response. Mechanistically, IRF8 expression is associated with a modulated tumor immune microenvironment and improved immunotherapeutic response.