β-glucan restores tumor-educated dendritic cell maturation to enhance antitumor immune responses

Int J Cancer. 2016 Jun 1;138(11):2713-23. doi: 10.1002/ijc.30002. Epub 2016 Feb 8.

Abstract

Tumors can induce the generation and accumulation of immunosuppressive cells such as myeloid-derived suppressor cells (MDSCs) in a tumor microenvironment, contributing to tumor escape from immunological attack. Although dendritic cell-based cancer vaccines can initiate antitumor immune responses, tumor-educated dendritic cells (TEDCs) involved in the tolerance induction have attracted much attention recently. In this study, we investigated the effect of β-glucan on TEDCs and found that β-glucan treatment could promote the maturation and migration of TEDCs and that the suppressive function of TEDCs was significantly decreased. Treatment with β-glucan drastically decreased the levels of regulatory T (Treg) cells but increased the infiltration of macrophages, granulocytes and DCs in tumor masses, thus elicited Th1 differentiation and cytotoxic T-lymphocyte responses and led to a delay in tumor progression. These findings reveal that β-glucan can inhibit the regulatory function of TEDCs, therefore revealing a novel function for β-glucan in immunotherapy and suggesting its potential clinical benefit. β-Glucan directly abrogated tumor-educated dendritic cells-associated immune suppression, promoted Th1 differentiation and cytotoxic T-lymphocyte priming and improved antitumor responses.

Keywords: T cell differentiation; dendritic cell; immune suppression; tumor immunotherapy; β-Glucan.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cancer Vaccines / immunology*
  • Cancer Vaccines / therapeutic use
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Dendritic Cells / cytology
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Humans
  • Immunity, Cellular*
  • Immunotherapy
  • Macrophages / immunology
  • Myeloid Cells / immunology*
  • Neoplasms / immunology*
  • Neoplasms / therapy
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Regulatory / immunology
  • Tumor Microenvironment / immunology
  • beta-Glucans / immunology
  • beta-Glucans / pharmacology

Substances

  • Cancer Vaccines
  • beta-Glucans