Introduction

Pancreatic cancer shows a high mortality rate due to difficulties in early diagnosis and the absence of standardized guidelines for assessing suspicious pancreatic masses. Biomarkers such as carcinoembryonic antigen (CEA) and CA19-9 lack sufficient sensitivity and specificity for pancreatic cancer detection. While tissue biopsy provides a static signature of target protein expressions, including PD-L1, the enumeration and profiling of circulating tumor cells (CTCs) with cell surface markers can offer actionable targets for treatment. We present findings in pancreatic cancer where CTCs are associated with overexpression of PD-L1 as a dynamic marker for monitoring minimal residual disease (MRD) and disease progression, highlighting its role in the metastatic cascade.

Methods

Retrospectively, 50 pancreatic cancer patients were investigated for the presence of CTCs. Among them, 12 patients (24%) were in the early stage of disease, with ages ranging from 35 to 75 years. Sixty percent of patients were male (n = 30) and 40% were female (n = 20), while 76% (n = 38) were classified as late-stage cases. PD-L1 expression was evaluated using the approved OncoDiscover platform, which utilizes multi-component systems conjugated with anti-EpCAM antibodies on magnetic nanoparticles. CTC enumeration was performed using CD45–, EpCAM+, DAPI+, and CK18+ markers in 1.5 ml of peripheral blood. Functional assays assessed PD-L1 overexpression on CTCs using automated motorized Zeiss fluorescence microscopy. The sensitivity of the CTC and PD-L1 assay had been previously evaluated in other solid cancers.

Results

Out of 50 pancreatic cancer patients, 74% (n = 37) had at least one detectable CTC. Among these patients, 51% (n = 19) had one CTC, 30% (n = 11) had two CTCs, 14% (n = 5) had three CTCs, and 5% (n = 2) had four CTCs. The mean number of CTCs and clusters was 1.28 and 0.16, respectively. Additionally, 92% (n = 34) of patients demonstrated PD-L1 expression on CTCs. CTC clusters were observed in 19% of patients (n = 7). The mean PD-L1 expression on CTCs was 1.14.

Conclusions

CTCs with PD-L1 overexpression strongly suggest poor prognosis, potentially linked to activation of the metastatic cascade through immune system evasion. Larger studies are required to validate whether PD-L1-positive CTCs can serve as a reliable biomarker for the diagnosis and management of pancreatic cancer.