TY - JOUR
T1 - Mature dendritic cells correlate with favorable immune infiltrate and improved prognosis in ovarian carcinoma patients
AU - Truxova, Iva
AU - Kasikova, Lenka
AU - Hensler, Michal
AU - Skapa, Petr
AU - Laco, Jan
AU - Pecen, Ladislav
AU - Belicova, Lucie
AU - Praznovec, Ivan
AU - Halaska, Michael J.
AU - Brtnicky, Tomas
AU - Salkova, Eva
AU - Rob, Lukas
AU - Kodet, Roman
AU - Goc, Jeremy
AU - Sautes-Fridman, Catherine
AU - Fridman, Wolf Herman
AU - Ryska, Ales
AU - Galluzzi, Lorenzo
AU - Spisek, Radek
AU - Fucikova, Jitka
N1 - Publisher Copyright:
© 2018 The Author(s).
PY - 2018/12/4
Y1 - 2018/12/4
N2 - 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.
AB - 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.
KW - CD8 cytotoxic T lymphocytes
KW - DC-LAMP
KW - Dendritic cells
KW - Natural killer cells
KW - Tertiary lymphoid structures
UR - http://www.scopus.com/inward/record.url?scp=85058319459&partnerID=8YFLogxK
U2 - 10.1186/s40425-018-0446-3
DO - 10.1186/s40425-018-0446-3
M3 - Article
C2 - 30526667
AN - SCOPUS:85058319459
SN - 2051-1426
VL - 6
JO - Journal for ImmunoTherapy of Cancer
JF - Journal for ImmunoTherapy of Cancer
IS - 1
M1 - 139
ER -
