PD-L1 and Notch as novel biomarkers in pancreatic sarcomatoid carcinoma: a pilot study
| Autor: | Nicola Silvestris, Fulvia Colonna, Antonio Giovanni Solimando, Sabina Delcuratolo, Concetta Saponaro, Aldo Scarpa, Livia Fucci, Margherita Sonnessa, Claudio Luchini, Floriana Nappo, Antonella Argentiero, Sara Lonardi, Matteo Fassan, Oronzo Brunetti |
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| Rok vydání: | 2021 |
| Předmět: |
PD-L1
Notch Clinical Biochemistry Pilot Projects Biology Immunofluorescence B7-H1 Antigen Immunophenotyping Immune system Pancreatic cancer Drug Discovery Biomarkers Tumor Tumor Microenvironment medicine Humans Receptor Notch1 Sarcomatoid carcinoma Receptor Notch3 rare pancreatic carcinoma Retrospective Studies Pharmacology Tumor microenvironment pancreatic sarcomatoid carcinoma medicine.diagnostic_test pd-l1 medicine.disease Pancreatic Neoplasms Cancer cell biology.protein Cancer research Molecular Medicine |
| Zdroj: | Expert Opinion on Therapeutic Targets. 25:1007-1016 |
| ISSN: | 1744-7631 1472-8222 |
| DOI: | 10.1080/14728222.2021.2011859 |
| Popis: | Background The improved immunological understanding revealed the tumor microenvironment as an appealing driver to restore the immune response against cancer cells resulting in a paradigm shift in the oncology field. However, the complexity of the tumor milieu suggests a role of several pathways linking in immunomodulation mechanisms. Pancreatic cancer represents a model of the intricate relationship between malignant cells and their surrounding neighborhood. Research design and methods In this study we analyzed, retrospectively, 6 cases of rare pancreatic sarcomatoid carcinoma (PSC) and evaluated the expression of PD-L1 and Notch, aiming to explore new attributes in immunophenotype. Results PD-L1 CPS≥1% was common in PSCs (83%) with half samples expressing PD-L1 CPS≥50%. Notch1 and Notch3 expression resulted positive demonstrating a high IRS range of expression. A direct significant correlation between PD-L1 and Nocth3 overexpression (r=0.7; p=0.036) has been observed. Moreover, immunofluorescence studies revealed a co-localization of Notch3 and PD-L1 when both proteins were over-expressed within cytoplasmic or membranous compartments of the same cells. Conclusions Our data identify a unique biological characterization of this rare pancreatic histotype. These findings provide a rationale for future studies evaluating the potential crosstalk between PD-L1/PD-1 axis and Notch pathways and prompting the development of novel therapeutics strategy. |
| Databáze: | OpenAIRE |
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