PD-L1 Expression in Colorectal Adenocarcinoma Is Associated With the Tumor Immune Microenvironment and Epithelial-Mesenchymal Transition

Abstract

Objectives: Colorectal carcinomas are the third-most common tumors in the world, and colorectal cancer ranks second in cancer-related deaths. Our aim in this study was to investigate the correlation between programmed cell death ligand 1 (PD-L1) expression and clinicopathologic parameters in colorectal carcinomas and their relationship to the tumor immune microenvironment, epithelial-mesenchymal transition (EMT), and microsatellite instability. We also investigated the predictive and prognostic role of PD-L1.

Methods: One hundred patients with a diagnosis of colorectal adenocarcinoma who did not receive neoadjuvant therapy were included in the study. The relationships among the altered expression of PD-L1; vimentin; E-cadherin; mismatch repair status; and pathologic microenvironmental features, including the presence of tumor budding and CD8-positive tumor infiltrating lymphocytes (TILs), were assessed.

Results: Increased PD-L1 expression in tumor cells was associated with increased TILs (P = .013), high histologic grade (P = .011), advanced pathologic T stage (P = .007), lymph node metastasis (P = .002), distant metastasis (P < .001), perineural invasion (P = .009), high bud score (P = .023), EMT (P < .001), and shorter disease-free survival (P = .029).

Conclusions: Overall, PD-L1 expression in colorectal carcinoma tumor cells is a marker of poor prognosis, and the positive correlation detected between EMT status and PD-L1 expression suggests that patients with the mesenchymal phenotype may be more likely to benefit from programmed cell death 1 protein/PD-L1 immunotherapy.

Keywords: Colorectal cancer; Epithelial-mesenchymal transition; Prognosis; Program cell death ligand 1; Tumor budding.