Paramunity-inducing Factors (PINDs) in dendritic cell (DC) cultures lead to impaired antileukemic functionality of DC-stimulated T-cells

Christian Ansprenger, Valentin Vogt, Julia Schick, Annika Hirn-Lopez, Yvonne Vokac, Ihor Harabacz, Marion Braeu, Tanja Kroell, Axel Karenberg, Hans Jochem Kolb, Helga Schmetzer

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Introduction: Paramunity-inducing-Factors (PINDs) consist of attenuated/inactivated viruses of various poxvirus-genera, used in veterinary medicine as non-antigen-specific, non-immunising stimulators of the innate immune system against infectious and malignant diseases. Their danger-signaling-interactions were tested for their capacity to improve leukemic antigen-presentation on DC generated from AML-patients’ blasts (‘DCleu’) and DC-stimulation/activation of antileukemic T-cells. Methods: We analyzed, whether the addition of PINDs during DC cultures (15 healthy, 22 leukemic donors) and mixed lymphocyte culture (MLC, n = 15) with autologous (n = 6), allogeneic (n = 2) or T-cells after stem cell transplantation (SCT; n = 7) would alter the quality and quantity of DC, the composition of T-cell-subsets, and/or their antileukemic functionality (AF) as studied by FACS and functional Fluorolysis-cytotoxicity-assays. Results: Effects on 1. DC-cultures: PINDs in DC-cultures lead to increased proportions of mature DC and DCleu, but reduced proportions of viable and overall, as well as TLR4- and TLR9-expressing DC. 2. MLC: PINDs increased early (CD8+) T-cell activation (CD69+), but reduced proportions of effector-T-cells after MLC 3. AF: Presence of PINDs in DC- and MLC-cultures reduced T-cells’ as well as innate cells’ antileukemic functionality. 4. Cytokine-release profile: Supernatants from PIND-treated DC- and MLC-cultures resembled an inhibitory microenvironment, correlating with impaired blast lysis. Conclusions: Our data shows that addition of PINDs to DC-cultures and MLC result in a “blast-protective-capacity” leading to impaired AF, likely due to changes in the composition of T-/innate effector cells and the induction of an inhibitory microenvironment. PINDs might be promising in treating infectious diseases, but cannot be recommended for the treatment of AML-patients due to their inhibitory influence on antileukemic functionality.

Original languageEnglish
Pages (from-to)33-48
Number of pages16
JournalCellular Immunology
Volume328
DOIs
StatePublished - Jun 2018
Externally publishedYes

Keywords

  • AML
  • Dendritic cells
  • Immunotherapy
  • PIND
  • Paramunity
  • T-cells
  • Zylexis

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