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

J Immunother Cancer. 2018 Dec 4;6(1):139. doi: 10.1186/s40425-018-0446-3.

Abstract

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.

Keywords: CD8+ cytotoxic T lymphocytes; DC-LAMP; Dendritic cells; Natural killer cells; Tertiary lymphoid structures.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers
  • Carcinoma / immunology*
  • Carcinoma / mortality
  • Carcinoma / pathology*
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Dendritic Cells / pathology*
  • Female
  • Humans
  • Immunohistochemistry
  • Immunophenotyping
  • Kaplan-Meier Estimate
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Middle Aged
  • Neoplasm Staging
  • Ovarian Neoplasms / immunology*
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / pathology*
  • Ovarian Neoplasms / therapy
  • Prognosis
  • Proportional Hazards Models
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocyte Subsets / pathology
  • Tumor Microenvironment / immunology*

Substances

  • Biomarkers