HLA class I expression and tumor immune infiltration together shape colon cancer immune contexture.

Abstract

BACKGROUND: The relative contribution of HLA class I molecules-including classical HLA class Ia (HLA-A, -B, -C) and non-classical HLA class Ib (HLA-E, -F, -G)-to shaping the tumor immune microenvironment in colon cancer remains insufficiently defined. We investigated how their expression patterns relate to immune infiltration and clinical outcome. METHODS: In a retrospective cohort of 280 colon cancers, we assessed HLA class Ia and class Ib expression and quantified CD45-positive immune cell infiltration by immunohistochemistry. These features were correlated with clinicopathological variables, microsatellite instability (MSI) status, and previously established genomic immune signatures. RESULTS: High HLA class Ia expression and increased CD45-positive cell infiltration were each associated with improved overall, disease-specific, and progression-free survival. CD45-positive density correlated strongly with Immunologic Constant of Rejection scores. HLA class Ia loss was more frequent in advanced stages and in MSI-H tumors. Among HLA class Ib molecules, only HLA-E expression was associated with favorable disease-specific and progression-free survival. Integrative analysis identified three immune phenotypes with distinct prognostic profiles; tumors characterized by high HLA class Ia expression, low HLA class Ib expression, and high CD45-positive infiltration had the best outcomes. CONCLUSION: Colon cancer immunogenicity is shaped by coordinated patterns of HLA class I expression and immune infiltration. Integrating HLA class Ia/Ib expression with immune cell density provides a refined stratification of tumor immune phenotypes and may support personalized immunotherapeutic decision-making.