PD-L1-positive circulating tumor cells associate with tumor malignancy and impaired circulating immunity in patients with gastrointestinal tumors

Abstract

Abstract Immunotherapies such as anti–PD-L1 antibodies have transformed cancer treatment, but their effectiveness in gastrointestinal tumors remains limited. One reason may be the absence of reliable prognostic markers that can identify patients at risk and those likely to benefit from such therapies. Circulating tumor cells (CTCs) have therefore gained attention as potential clinical markers for assessing tumor burden and immune status. In this study, 105 patients with esophageal, gastric, or colorectal cancer were enrolled preoperatively. CTCs were isolated and enumerated from venous blood using CellSearch, and PD-L1 expression was assessed. Lymphocytes were enriched via Percoll gradient centrifugation and analyzed by multiparametric flow cytometry. Statistical associations were evaluated using Chi-square tests. CTCs were detected in 16.2% of patients, and among these, 35.3% exhibited PD-L1 + CTCs. The presence of PD-L1 + CTCs correlated with indicators of advanced disease, including tumor stage, metastasis, and vascular invasion. Additionally, patients who were CTC-positive, and especially those with PD-L1 + CTCs, showed reduced immunocompetence, reflected by lower immune cell frequencies, suggesting a weakened systemic immune response. These findings indicate that PD-L1 + CTCs reflect tumor-driven immune suppression and may facilitate metastatic spread. Therefore, PD-L1 + CTCs should be considered as promising prognostic biomarkers and may provide a rationale for early immunotherapy.