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

Area of Science:

• Oncology
• Immunology
• Genomics

Background:

• Solid subtype adenocarcinomas are associated with poor prognosis.
• Interferon-gamma (IFN-γ) is a key cytokine in anti-tumor immune responses within the tumor microenvironment.
• Identifying factors influencing IFN-γ responsiveness is crucial for understanding and improving treatment outcomes.

Purpose of the Study:

• To identify prognostic factors associated with IFN-γ responsiveness in lung adenocarcinoma.
• To elucidate the genomic profile and prognostic implications of IFN-γ pathway expression in different lung adenocarcinoma subtypes.

Main Methods:

• Analysis of 112 lung adenocarcinoma samples (surgery, 2014-2020) including DNA and RNA extraction.
• Utilized The Cancer Genome Atlas dataset for comparative analysis.
• Classified adenocarcinomas based on IFN-γ response pathway expression using single-sample gene set enrichment analysis.

Main Results:

• Solid subtype adenocarcinomas exhibit a more immunologically active microenvironment.
• Lower IFN-γ response pathway expression (GOBP-IFNG low) correlated with poorer overall survival (OS) in the solid subtype.
• Low GOBP-IFNG levels were identified as an independent poor prognostic factor, associated with reduced apoptosis, lower MHC class II expression, and higher copy number alterations.

Conclusions:

• Solid subtype adenocarcinomas are characterized by significant immune cell infiltration.
• IFN-γ response pathway expression is a significant prognostic indicator for overall survival in solid subtype lung adenocarcinoma.
• Understanding IFN-γ pathway expression may offer novel strategies for improving prognosis in these patients.