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Circulating Cancer Associated Macrophage-like Cells as a Potential New Prognostic Marker in Pancreatic Ductal Adenocarcinoma

Affiliation
Department of General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf, 20246 Hamburg, Germany
Nitschke, Christine;
ORCID
0000-0003-3602-1607
Affiliation
Department of General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf, 20246 Hamburg, Germany
Markmann, Benedikt;
ORCID
0000-0001-7674-1276
Affiliation
Department of General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf, 20246 Hamburg, Germany
Konczalla, Leonie;
Affiliation
Department of Tumor Biology, University Hospital Hamburg-Eppendorf, 20246 Hamburg, Germany
Kropidlowski, Jolanthe;
Affiliation
Department of Tumor Biology, University Hospital Hamburg-Eppendorf, 20246 Hamburg, Germany
Pereira-Veiga, Thais;
Affiliation
Department of General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf, 20246 Hamburg, Germany
Scognamiglio, Pasquale;
Affiliation
II Medical Clinic and Polyclinic (Oncology), University Hospital Hamburg-Eppendorf, 20246 Hamburg, Germany
Schönrock, Martin;
Affiliation
II Medical Clinic and Polyclinic (Oncology), University Hospital Hamburg-Eppendorf, 20246 Hamburg, Germany
Sinn, Marianne;
Affiliation
Department of General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf, 20246 Hamburg, Germany
Tölle, Marie;
Affiliation
Department of General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf, 20246 Hamburg, Germany
Izbicki, Jakob;
ORCID
0000-0001-5736-2772
Affiliation
Department of Tumor Biology, University Hospital Hamburg-Eppendorf, 20246 Hamburg, Germany
Pantel, Klaus;
ORCID
0000-0002-6890-4829
Affiliation
Department of General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf, 20246 Hamburg, Germany
Uzunoglu, Faik G.;
ORCID
0000-0001-6862-0888
Affiliation
Department of Tumor Biology, University Hospital Hamburg-Eppendorf, 20246 Hamburg, Germany
Wikman, Harriet

Background: Circulating Cancer Associated Macrophage-like cells (CAMLs) have been described as novel liquid biopsy analytes and unfavorable prognostic markers in some tumor entities, with scarce data for Pancreatic Ductal Adenocarcinomas (PDAC). Methods: Baseline and follow-up blood was drawn from resected curative ( n = 36) and palliative ( n = 19) PDAC patients. A microfluidic size-based cell enrichment approach (Parsortix TM ) was used for CAML detection, followed by immunofluorescence staining using pan-keratin, CD14, and CD45 antibodies to differentiate between CAMLs, circulating tumor cells (CTCs), and leukocytes. Results: CAMLs were detectable at baseline in 36.1% of resected patients and 47.4% of palliative PDAC patients. CAML detection was tumor stage independent. Follow-up data indicated that detection of CAMLs (in 45.5% of curative patients) was an independent prognostic factor for shorter recurrence-free survival (RFS) (HR: 4.3, p = 0.023). Furthermore, a combined analysis with CTCs showed the detectability of at least one of these cell populations in 68.2% of resected patients at follow-up. The combined detection of CAMLs and CTCs was also significantly associated with short RFS (HR: 8.7, p = 0.003). Conclusions: This pilot study shows that detection of CAMLs in PDAC patients can provide prognostic information, either alone or even more pronounced in combination with CTCs, which indicates the power of liquid biopsy marker analyses.

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