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

0523722 - ÚI 2021 US eng A - Abstract
Truxová, I. - Kašíková, L. - Hensler, M. - Skapa, P. - Laco, J. - Pecen, Ladislav - Belicová, L. - Vošahlíková, Š. - Práznovec, I. - Halaška, M. - Brtnický, T. - Šálková, E. - Rob, L. - Kodet, R. - Goc, J. - Sautes-Fridman, C. - Fridman, W. H. - Ryška, A. - Galluzzi, L. - Špíšek, R. - Fučíková, J.
Mature dendritic cells correlate with favorable immune infiltrate and improved prognosis in ovarian carcinoma patients.
Cancer Immunology Research. Roč. 8, 3 Supplement (2020), A24-A24. ISSN 2326-6066. E-ISSN 2326-6074.
[2019 AACR Meeting on Tumor Immunology and Immunotherapy. 17.11.2019-20.11.2019, Boston]
https://cancerimmunolres.aacrjournals.org/content/8/3_Supplement/A24

A high density of tumor-infiltrating CD8+ T lymphocytes (CTLs), key mediator of anticancer immunity, and CD20+ B cells correlates with positive prognostic value and prolonged survival in patients with a various solid tumors including high-grade serous ovarian carcinoma (HGSC). The majority of HGSCs containing high frequencies of CD8+ CTLs are also robustly infiltrated by CD20+ B cells, and patients whose tumors exhibit abundant coinfiltration have higher survival rates than patients with tumors that only contain high amounts of CD8+ CTLs. However, the cellular mechanism, 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. Three independent cohorts of patients with resectable HGSC who did not receive neoadjuvant chemotherapy were involved in the study. Lysosomal-associated membrane protein 3 (DC-LAMP) and its colocalization with CD20+B cells in samples was analyzed by immunohistochemistry (IHC) and cell quantification. Prognostic impact of DC-LAMP+ cells in patient cohort was stratified based on median density of DC-LAMP+ cells in the tumor stroma and nest, followed by retrospective RFS and OS analysis. Comparison of DC-LAMPHi and DC-LAMPLo patients and impact of mature DCs on the composition of the immune contexture characterized by TH1 polarization and cytotoxic activity was performed by biomolecular analyses (flow cytometry, NGS analysis). Patients with high density of DC-LAMP+ cells in the tumor stroma exhibited significantly longer RFS and OS than DC-LAMP- patients. Compared to DC-LAMPLo, DC-LAMPHi tumors exhibited an over-representation of gene sets specifically clustering to the following immunologic functions: T cells, CD8 cytotoxicity, TH1 polarization, T cell activation, NK cells, and plasma cells. Also, a significantly higher percentage of CD3+CD45+ and CD3+CD8+ T cells among live mononuclear cells and higher density of NK cells in the tumor stroma in DC-LAMPHi were observed. We found 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. Robust tumor infiltration by both DC-LAMP+ DCs and CD20+ B cells was associated with most favorable overall survival in independent cohorts of chemotherapy-naive 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.
Permanent Link: http://hdl.handle.net/11104/0308026