Arginase-1 in Plasma-Derived Exosomes as Marker of Metastasis in Patients with Head and Neck Squamous Cell Carcinoma

Immunoregulatory Arginase-1 (Arg-1) is present in the tumor microenvironment of solid tumors. Its association to clinicopathology and its prognostic impact are inconsistent among different tumor types and biological fluids. This study evaluated Arg-1 protein levels in tumors and the circulation of p...

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Bibliographic Details
Published in:Cancers 2023-11, Vol.15 (22), p.5449
Main Authors: Hofmann, Linda, Harasymczuk, Malgorzata, Huber, Diana, Szczepanski, Miroslaw J, Dworacki, Grzegorz, Whiteside, Theresa L, Theodoraki, Marie-Nicole
Format: Article
Language:English
Subjects:
Arginase
Cancer
Cell growth
Cell interactions
Enzyme-linked immunosorbent assay
Enzymes
Ethics
Exosomes
Extracellular vesicles
Head & neck cancer
Head and neck carcinoma
Immunohistochemistry
Immunoregulation
Immunosuppression
Immunotherapy
Lymph nodes
Metastases
Metastasis
Otolaryngology
Plasma
Polyamines
Prognosis
Proteins
Solid tumors
Squamous cell carcinoma
Surgery
Tumor microenvironment
Tumors
Western blotting
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Summary:Immunoregulatory Arginase-1 (Arg-1) is present in the tumor microenvironment of solid tumors. Its association to clinicopathology and its prognostic impact are inconsistent among different tumor types and biological fluids. This study evaluated Arg-1 protein levels in tumors and the circulation of patients with head and neck squamous cell carcinoma (HNSCC) in relation to clinical stage and prognosis. Tumor Arg-1 expression was monitored via immunohistochemistry while plasma Arg-1 levels via ELISA in 37 HNSCC patients. Arg-1 presence in plasma-derived exosomes was assessed using Western blots in 20 HNSCC patients. High tumor Arg-1 expression correlated with favorable clinicopathology and longer recurrence-free survival (RFS), while high plasma Arg-1 levels were associated with unfavorable clinicopathology. All patients with low tumor and high plasma Arg-1 had nodal metastases and developed recurrence. This discrepancy was attributed to the presence of Arg-1-carrying exosomes. Arg-1 was found in plasma-derived exosomes from all HNSCC patients. High exosomal Arg-1 levels were associated with positive lymph nodes and short RFS. Circulating Arg-1 exosomes represent a mechanism of active Arg-1 export from the tumor to the periphery. Exosomes reflected biologically relevant Arg-1 levels in metastatic HNSCC and emerged as potentially more accurate biomarkers of metastatic disease and RFS than tissue or plasma Arg-1 levels.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers15225449