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Mature dendritic cells correlate with favorable immune infiltrate and improved prognosis in ovarian carcinoma patients

I. Truxova, L. Kasikova, M. Hensler, P. Skapa, J. Laco, L. Pecen, L. Belicova, I. Praznovec, MJ. Halaska, T. Brtnicky, E. Salkova, L. Rob, R. Kodet, J. Goc, C. Sautes-Fridman, WH. Fridman, A. Ryska, L. Galluzzi, R. Spisek, J. Fucikova,

. 2018 ; 6 (1) : 139. [pub] 20181204

Language English Country Great Britain

Document type Journal Article, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc19045097

A high density of tumor-infiltrating CD8+ T cells and CD20+ B cells correlates with prolonged survival in patients with a wide variety of human cancers, including high-grade serous ovarian carcinoma (HGSC). However, the potential impact of mature dendritic cells (DCs) in shaping the immune contexture of HGSC, their role in the establishment of T cell-dependent antitumor immunity, and their potential prognostic value for HGSC patients remain unclear. We harnessed immunohistochemical tests and biomolecular analyses to demonstrate that a high density of tumor-infiltrating DC-LAMP+ DCs is robustly associated with an immune contexture characterized by TH1 polarization and cytotoxic activity. We showed that both mature DCs and CD20+ B cells play a critical role in the generation of a clinically-favorable cytotoxic immune response in HGSC microenvironment. In line with this notion, robust tumor infiltration by both DC-LAMP+ DCs and CD20+ B cells was associated with most favorable overall survival in two independent cohorts of chemotherapy-naïve HGSC patients. Our findings suggest that the presence of mature, DC-LAMP+ DCs in the tumor microenvironment may represent a novel, powerful prognostic biomarker for HGSC patients that reflects the activation of clinically-relevant anticancer immunity.

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$a Truxova, Iva $u Department of Immunology, Charles University, 2nd Faculty of Medicine and University Hospital Motol, Prague, Czech Republic. Sotio, Prague, Czech Republic.
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$a Mature dendritic cells correlate with favorable immune infiltrate and improved prognosis in ovarian carcinoma patients / $c I. Truxova, L. Kasikova, M. Hensler, P. Skapa, J. Laco, L. Pecen, L. Belicova, I. Praznovec, MJ. Halaska, T. Brtnicky, E. Salkova, L. Rob, R. Kodet, J. Goc, C. Sautes-Fridman, WH. Fridman, A. Ryska, L. Galluzzi, R. Spisek, J. Fucikova,
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$a A high density of tumor-infiltrating CD8+ T cells and CD20+ B cells correlates with prolonged survival in patients with a wide variety of human cancers, including high-grade serous ovarian carcinoma (HGSC). However, the potential impact of mature dendritic cells (DCs) in shaping the immune contexture of HGSC, their role in the establishment of T cell-dependent antitumor immunity, and their potential prognostic value for HGSC patients remain unclear. We harnessed immunohistochemical tests and biomolecular analyses to demonstrate that a high density of tumor-infiltrating DC-LAMP+ DCs is robustly associated with an immune contexture characterized by TH1 polarization and cytotoxic activity. We showed that both mature DCs and CD20+ B cells play a critical role in the generation of a clinically-favorable cytotoxic immune response in HGSC microenvironment. In line with this notion, robust tumor infiltration by both DC-LAMP+ DCs and CD20+ B cells was associated with most favorable overall survival in two independent cohorts of chemotherapy-naïve HGSC patients. Our findings suggest that the presence of mature, DC-LAMP+ DCs in the tumor microenvironment may represent a novel, powerful prognostic biomarker for HGSC patients that reflects the activation of clinically-relevant anticancer immunity.
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$a Kasikova, Lenka $u Department of Immunology, Charles University, 2nd Faculty of Medicine and University Hospital Motol, Prague, Czech Republic. Sotio, Prague, Czech Republic.
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$a Hensler, Michal $u Sotio, Prague, Czech Republic.
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$a Skapa, Petr $u Department of Pathology and Molecular Medicine, Charles University, 2nd Faculty of Medicine and University Hospital Motol, Prague, Czech Republic.
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$a Laco, Jan $u The Fingerland Department of Pathology, Charles University, Faculty of Medicine and University Hospital Hradec Kralove, Hradec Kralove, Czech Republic.
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$a Pecen, Ladislav $u Sotio, Prague, Czech Republic.
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$a Belicova, Lucie $u Sotio, Prague, Czech Republic.
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$a Praznovec, Ivan $u Department of Gynecology and Obstetrics, Charles University, Faculty of Medicine and University Hospital Hradec Kralove, Hradec Kralove, Czech Republic.
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$a Halaska, Michael J $u Department of Gynecology and Obstetrics, Charles University, 3rd Faculty of Medicine and University Hospital Kralovske Vinohrady, Prague, Czech Republic.
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$a Brtnicky, Tomas $u Department of Gynecology and Obstetrics, Charles University, 2nd Faculty of Medicine and University Hospital Motol, Prague, Czech Republic.
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$a Salkova, Eva $u Department of Pathology and Molecular Medicine, Charles University, 2nd Faculty of Medicine and University Hospital Motol, Prague, Czech Republic.
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$a Rob, Lukas $u Department of Gynecology and Obstetrics, Charles University, 3rd Faculty of Medicine and University Hospital Kralovske Vinohrady, Prague, Czech Republic.
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$a Kodet, Roman $u Department of Pathology and Molecular Medicine, Charles University, 2nd Faculty of Medicine and University Hospital Motol, Prague, Czech Republic.
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$a Goc, Jeremy $u INSERM, U1138, Centre de Recherche des Cordeliers, Paris, France. Sorbonne Université, Paris, France. Université Paris Descartes/Paris V, Paris, France.
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$a Sautes-Fridman, Catherine $u INSERM, U1138, Centre de Recherche des Cordeliers, Paris, France. Sorbonne Université, Paris, France. Université Paris Descartes/Paris V, Paris, France.
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$a Fridman, Wolf Herman $u INSERM, U1138, Centre de Recherche des Cordeliers, Paris, France. Sorbonne Université, Paris, France. Université Paris Descartes/Paris V, Paris, France.
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$a Ryska, Ales $u The Fingerland Department of Pathology, Charles University, Faculty of Medicine and University Hospital Hradec Kralove, Hradec Kralove, Czech Republic.
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$a Galluzzi, Lorenzo $u Université Paris Descartes/Paris V, Paris, France. Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, USA. Sandra and Edward Meyer Cancer Center, New York, NY, USA.
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$a Spisek, Radek $u Department of Immunology, Charles University, 2nd Faculty of Medicine and University Hospital Motol, Prague, Czech Republic. Sotio, Prague, Czech Republic.
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$a Fucikova, Jitka $u Department of Immunology, Charles University, 2nd Faculty of Medicine and University Hospital Motol, Prague, Czech Republic. fucikova@sotio.com. Sotio, Prague, Czech Republic. fucikova@sotio.com.
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