Tumor Immune Microenvironment Biomarkers for Recurrence Prediction in Locally Advanced Rectal Cancer Patients after...

Area of Science:

• Oncology
• Immunology
• Pathology

Background:

• The tumor microenvironment (TME) is a critical prognostic factor in cancer.
• Identifying prognostic biomarkers is essential for locally advanced rectal cancer (LARC) patients undergoing neoadjuvant chemoradiotherapy (nCRT).

Purpose of the Study:

• To identify prognostic factors by integrating clinicopathologic parameters and TME biomarkers in LARC patients post-nCRT.
• To evaluate the association between TME biomarkers, clinicopathologic features, and survival outcomes.

Main Methods:

• Immunohistochemical staining for CD8+ T cells, CXCR3, CXCL10, and α-smooth muscle actin (α-SMA).
• AI-powered digital pathology for spatial TME assessment.
• Correlation analysis of biomarkers with clinicopathologic parameters and survival.

Main Results:

• High CD8+ T cell expression and CXCR3 in tumor-infiltrating lymphocytes (TILs) correlated with an inflamed TME and better prognosis.
• CD8+ T cells and inflamed/immune-excluded phenotypes were significant biomarkers for recurrence-free survival (RFS) but not overall survival (OS).
• Immune-desert phenotype indicated poor prognosis irrespective of pathologic stage or adjuvant chemotherapy.

Conclusions:

• CD8+ T cells and AI-derived immune phenotypes, combined with clinical factors, can personalize treatment for LARC patients receiving nCRT.
• Modifying the TME post-nCRT may offer a therapeutic strategy to decrease surgical recurrence.