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| Item Type: | Article |
|---|---|
| Title: | Elevated Flt3L predicts long-term survival in patients with high-grade gastroenteropancreatic neuroendocrine neoplasms |
| Creators Name: | Detjen, K.M., Otto, R., Giesecke, Y., Geisler, L., Riemer, P., Jann, H., Grötzinger, C., Sers, C., Pascher, A., Lüdde, T., Leser, U., Wiedenmann, B., Sigal, M., Tacke, F., Roderburg, C. and Hammerich, L. |
| Abstract: | BACKGROUND: The clinical management of high-grade gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) is challenging due to disease heterogeneity, illustrating the need for reliable biomarkers facilitating patient stratification and guiding treatment decisions. FMS-like tyrosine kinase 3 ligand (Flt3L) is emerging as a prognostic or predictive surrogate marker of host tumoral immune response and might enable the stratification of patients with otherwise comparable tumor features. METHODS: We evaluated Flt3L gene expression in tumor tissue as well as circulating Flt3L levels as potential biomarkers in a cohort of 54 patients with GEP-NEN. RESULTS: We detected a prominent induction of Flt3L gene expression in individual G2 and G3 NEN, but not in G1 neuroendocrine tumors (NET). Flt3L mRNA expression levels in tumor tissue predicted the disease-related survival of patients with highly proliferative G2 and G3 NEN more accurately than the conventional criteria of grading or NEC/NET differentiation. High level Flt3L mRNA expression was associated with the increased expression of genes related to immunogenic cell death, lymphocyte effector function and dendritic cell maturation, suggesting a less tolerogenic (more proinflammatory) phenotype of tumors with Flt3L induction. Importantly, circulating levels of Flt3L were also elevated in high grade NEN and correlated with patients' progression-free and disease-related survival, thereby reflecting the results observed in tumor tissue. CONCLUSIONS: We propose Flt3L as a prognostic biomarker for high grade GEP-NEN, harnessing its potential as a marker of an inflammatory tumor microenvironment. Flt3L measurements in serum, which can be easily be incorporated into clinical routine, should be further evaluated to guide patient stratification and treatment decisions. |
| Keywords: | Neuroendocrine Neoplasm, Immuno-Oncology, Tumor Microenvironment, Circulating Biomarker, Flt3L, Cytokine |
| Source: | Cancers |
| ISSN: | 2072-6694 |
| Publisher: | MDPI |
| Volume: | 13 |
| Number: | 17 |
| Page Range: | 4463 |
| Date: | 1 September 2021 |
| Official Publication: | https://doi.org/10.3390/cancers13174463 |
| PubMed: | View item in PubMed |
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