PD-L1 Expression in High-Risk Early-Stage Colorectal Cancer-Its Clinical and Biological Significance in Immune...

Area of Science:

• Oncology
• Immunology
• Molecular Biology

Background:

• Programmed death-ligand 1 (PD-L1) is a key immune checkpoint molecule regulating anti-tumor immunity.
• The role of PD-L1 in early-stage colorectal cancer (CRC) and its associated immune responses requires further elucidation.

Purpose of the Study:

• To investigate the prognostic value of PD-L1 expression in early-stage CRC.
• To explore the relationship between PD-L1 expression and immune responses in the tumor microenvironment (TME) of CRC patients.

Main Methods:

• Immunohistochemical staining was used to assess PD-L1 expression (tumor proportion score and combined positive score) in a Taiwanese CRC cohort.
• Oncomine immune response assay and TCGA database analyses (GSEA) were employed to examine immune gene expression and PD-L1-associated pathways.

Main Results:

• High PD-L1 expression (CPS ≥ 5) correlated with significantly longer recurrence-free survival (p=0.031) and was an independent prognostic factor.
• High PD-L1 expression was associated with six immune-related gene signatures, with CXCL9 identified as the most significantly overexpressed gene.
• Elevated CXCL9 expression was linked to increased infiltration of CD8+ T lymphocytes and M1 macrophages in the TME.

Conclusions:

• High PD-L1 expression serves as a favorable prognostic indicator for early-stage colorectal cancer.
• CXCL9 may play a critical role in mediating the immune responses associated with PD-L1 expression in CRC.