The difference in tumor immune microenvironment and IFN-γ response between solid and non-solid adenocarcinoma

Solid subtype adenocarcinomas have poor prognosis. Interferon-γ (IFN-γ) is a critical cytokine related to anti-tumor response in the tumor immune microenvironment. We aimed to identify the prognostic factors related to IFN-γ responsiveness.

A total of 112 lung adenocarcinoma samples were obtained from patients who underwent surgery between 2014 and 2020. DNA and RNA were extracted and analyzed. Additionally, the Cancer Genome Atlas dataset of patients with lung cancer was accessed. We classified adenocarcinomas using single-sample gene set enrichment analysis based on IFN-γ response pathway expression to elucidate the genomic profile and prognosis.

The tumor immune microenvironment is immunologically hot, with higher immune cell infiltration in the solid subtype than in the non-solid subtype. The patients were divided into two groups [Gene Ontology Biological Process-Interferon-Gamma (GOBP-IFNG) high and low] according to IFN-γ response pathway expression. In the solid subtype, the GOBP-IFNG-low group showed poorer overall survival (OS) than the GOBP-IFNG-high group. Multivariate analysis demonstrated that low GOBP-IFNG level was an independent poor prognostic factor. The apoptosis score and MHC class II expression levels were lower in the low-GOBP-IFNG group than those in the high-GOBP-IFNG group. A proliferation assay using solid subtype adenocarcinoma cell lines demonstrated that one of the three cell lines did not respond to IFN-γ. The copy number alteration (CNA) in the low-GOBP-IFNG group was higher than that in the high-GOBP-IFNG group in the solid subtype.

Solid subtype adenocarcinomas are immunologically prevalent. IFN-γ response pathway expression is associated with the OS of solid subtype adenocarcinoma and may provide key insights to improve prognosis.