Immune Profiling of Vulvar Squamous Cell Cancer Discovers a Macrophage-rich Subtype Associated with Poor Prognosis.

Autor:	Condic M; Department of Gynecology and Gynecological Oncology, University Hospital Bonn, Bonn, Germany., Rohr A; Department of Gynecology and Gynecological Oncology, University Hospital Bonn, Bonn, Germany., Riemann S; Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Bonn, Germany., Staerk C; Department of Medical Biometry, Informatics and Epidemiology, University Hospital Bonn, Bonn, Germany., Ayub TH; Department of Gynecology and Gynecological Oncology, University Hospital Bonn, Bonn, Germany.; Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Bonn, Germany., Doeser A; Department of Gynecology and Gynecological Oncology, University Hospital Bonn, Bonn, Germany.; Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Bonn, Germany., Zillinger T; Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Bonn, Germany., Merkelbach-Bruse S; Institute of Pathology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany., Buettner R; Institute of Pathology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany., Barchet W; Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Bonn, Germany., Rudlowski C; Department of Gynecology and Gynecological Oncology, University Hospital Bonn, Bonn, Germany.; Lutherian Hospital, Academic Teaching Hospital of the University Hospital Bonn, Bergisch Gladbach, Germany., Mustea A; Department of Gynecology and Gynecological Oncology, University Hospital Bonn, Bonn, Germany., Kübler K; Department of Gynecology and Gynecological Oncology, University Hospital Bonn, Bonn, Germany.; Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Bonn, Germany.; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts.; Center for Cancer Research, Massachusetts General Hospital, Harvard Medical School Teaching Hospital, Charlestown, Massachusetts.; Center of Functional Genomics, Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, Berlin, Germany.; Department of Hematology, Oncology and Cancer Immunology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.; German Cancer Consortium (DKTK), Partner Site Berlin, and German Cancer Research Center (DKFZ), Heidelberg, Germany.
Jazyk:	angličtina
Zdroj:	Cancer research communications [Cancer Res Commun] 2024 Mar 21; Vol. 4 (3), pp. 861-875.
DOI:	10.1158/2767-9764.CRC-22-0366
Abstrakt:	The incidence rates of vulvar squamous cell cancer (VSCC) have increased over the past decades, requiring personalized oncologic approaches. Currently, lymph node involvement is a key factor in determining prognosis and treatment options. However, there is a need for additional immune-related biomarkers to provide more precise treatment and prognostic information. Here, we used IHC and expression data to characterize immune cells and their spatial distribution in VSCC. Hierarchical clustering analysis identified distinct immune subtypes, of which the macrophage-rich subtype was associated with adverse outcome. This is consistent with our findings of increased lymphogenesis, lymphatic invasion, and lymph node involvement associated with high macrophage infiltration. Further in vitro studies showed that VSCC-associated macrophages expressed VEGF-A and subsequently induced VEGF-A in the VSCC cell line A-431, providing experimental support for a pro-lymphangiogenic role of macrophages in VSCC. Taken together, immune profiling in VSCC revealed tumor processes, identified a subset of patients with adverse outcome, and provided a valuable biomarker for risk stratification and therapeutic decision making for anti-VEGF treatment, ultimately contributing to the advancement of precision medicine in VSCC. Significance: Immunoprofiling in VSCC reveals subtypes with distinct clinical and biological behavior. Of these, the macrophage-rich VSCC subtype is characterized by poor clinical outcome and increased VEGF-A expression, providing a biomarker for risk stratification and therapeutic sensitivity. (© 2024 The Authors; Published by the American Association for Cancer Research.)
Databáze:	MEDLINE
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