Tumor-associated neutrophils (TANs) in human carcinoma-draining lymph nodes: a novel TAN compartment.

Autor: Lonardi S; Section of Pathology Department of Molecular and Translational Medicine University of Brescia Brescia Italy.; ASST- Spedali Civili di Brescia Brescia Italy., Missale F; Unit of Otorhinolaryngology - Head and Neck Surgery Department of Surgical Specialties Radiological Sciences, and Public Health University of Brescia Brescia Italy.; IRCCS Ospedale Policlinico San Martino Unit of Otorhinolaryngology, Head and Neck Surgery Department of Surgical and Diagnostic Integrated Sciences University of Genoa Genoa Italy., Calza S; Unit of Biostatistics Department of Molecular and Translational Medicine University of Brescia Brescia Italy.; Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm Sweden.; Big&Open Data Innovation Laboratory University of Brescia Brescia Italy., Bugatti M; Section of Pathology Department of Molecular and Translational Medicine University of Brescia Brescia Italy.; ASST- Spedali Civili di Brescia Brescia Italy., Vescovi R; Section of Pathology Department of Molecular and Translational Medicine University of Brescia Brescia Italy., Debora B; Section of Pathology Department of Molecular and Translational Medicine University of Brescia Brescia Italy.; ASST- Spedali Civili di Brescia Brescia Italy., Uppaluri R; Department of Surgery/Otolaryngology Brigham and Women's Hospital and Dana-Farber Cancer Institute and Harvard Medical School Boston MA USA., Egloff AM; Department of Surgery/Otolaryngology Brigham and Women's Hospital and Dana-Farber Cancer Institute and Harvard Medical School Boston MA USA., Mattavelli D; Unit of Otorhinolaryngology - Head and Neck Surgery Department of Surgical Specialties Radiological Sciences, and Public Health University of Brescia Brescia Italy., Lombardi D; ASST- Spedali Civili di Brescia Brescia Italy.; Unit of Otorhinolaryngology - Head and Neck Surgery Department of Surgical Specialties Radiological Sciences, and Public Health University of Brescia Brescia Italy., Benerini Gatta L; Section of Pathology Department of Molecular and Translational Medicine University of Brescia Brescia Italy.; ASST- Spedali Civili di Brescia Brescia Italy., Marini O; Section of General Pathology Department of Medicine University of Verona Verona Italy., Tamassia N; Section of General Pathology Department of Medicine University of Verona Verona Italy., Gardiman E; Section of General Pathology Department of Medicine University of Verona Verona Italy., Cassatella MA; Section of General Pathology Department of Medicine University of Verona Verona Italy., Scapini P; Section of General Pathology Department of Medicine University of Verona Verona Italy., Nicolai P; ASST- Spedali Civili di Brescia Brescia Italy.; Unit of Otorhinolaryngology - Head and Neck Surgery Department of Surgical Specialties Radiological Sciences, and Public Health University of Brescia Brescia Italy., Vermi W; Section of Pathology Department of Molecular and Translational Medicine University of Brescia Brescia Italy.; ASST- Spedali Civili di Brescia Brescia Italy.; Department of Pathology and Immunology Washington University Saint Louis MO USA.
Jazyk: angličtina
Zdroj: Clinical & translational immunology [Clin Transl Immunology] 2021 Feb 16; Vol. 10 (2), pp. e1252. Date of Electronic Publication: 2021 Feb 16 (Print Publication: 2021).
DOI: 10.1002/cti2.1252
Abstrakt: Objectives: The role of tumor-associated neutrophils (TANs) in the nodal spread of cancer cells remains unexplored. The present study evaluates the occurrence and clinical significance of human nodal TANs.
Methods: The relevance, derivation, phenotype and interactions of nodal TANs were explored via a large immunohistochemical analysis of carcinoma-draining lymph nodes, and their clinical significance was evaluated on a retrospective cohort of oral squamous cell carcinomas (OSCC). The tumor-promoting function of nodal TAN was probed in the OSCC TCGA dataset combining TAN and epithelial-to-mesenchymal transition (EMT) signatures.
Results: The pan-carcinoma screening identified a consistent infiltration (59%) of CD66b +   TANs in tumor-draining lymph nodes (TDLNs). Microscopic findings, including the occurrence of intra-lymphatic conjugates of TANs and cancer cells, indicate that TANs migrate through lymphatic vessels. In vitro experiments revealed that OSCC cell lines sustain neutrophil viability and activation via release of GM-CSF. Moreover, by retrospective analysis, a high CD66b + TAN density in M-TDLNs of OSCC ( n  = 182 patients) predicted a worse prognosis. The analysis of the OSCC-TCGA dataset unveiled that the expression of a set of neutrophil-specific genes in the primary tumor (PT) is highly associated with an EMT signature, which predicts nodal spread. Accordingly, in the PT of OSCC cases, CD66b + TANs co-localised with PDPN + S100A9 - EMT-switched tumor cells in areas of lymphangiogenesis. The pro-EMT signature is lacking in peripheral blood neutrophils from OSCC patients, suggesting tissue skewing of TANs.
Conclusion: Our findings are consistent with a novel pro-tumoral TAN compartment that may promote nodal spread via EMT, through the lymphatics.
Competing Interests: The authors declare no competing financial interests.
(© 2021 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.)
Databáze: MEDLINE
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