December 4, 2018
Source: J Immunother Cancer. 2018 Dec 4;6(1):139. doi: 10.1186/s40425-018-0446-3.
Authors: I. Truxova, L. Kasikova, M. Hensler, P. Skapa, J. Laco, L. Pecen, L. Belicova, I. Praznovec, M.J. Halaska, T. Brtnicky, E. Salkova, L. Rob, R. Kodet, J. Goc, C. Sautes-Fridman, W.H. Fridman, A. Ryska, L.Galluzzi, R. Spisek, J. Fucikova
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.