CD137L-DCs, Potent Immune-Stimulators-History, Characteristics, and Perspectives.

Abstract:

:Dendritic cell (DC)-based immunotherapies are being explored for over 20 years and found to be very safe. Most often, granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4)-induced monocyte-derived DCs (moDCs) are being used, which have demonstrated some life-prolonging benefit to patients of multiple tumors. However, the limited clinical response and efficacy call for the development of more potent DCs. CD137L-DC may meet this demand. CD137L-DCs are a novel type of monocyte-derived inflammatory DCs that are induced by CD137 ligand (CD137L) agonists. CD137L is expressed on the surface of antigen-presenting cells, including monocytes, and signaling of CD137L into monocytes induces their differentiation to CD137L-DCs. CD137L-DCs preferentially induce type 1 T helper (Th1) cell polarization and strong type 1 CD8+ T cell (Tc1) responses against tumor-associated viral antigens. The in vitro T cell-stimulatory capacity of CD137L-DCs is superior to that of conventional moDCs. The transcriptomic profile of CD137L-DC is highly similar to that of in vivo DCs at sites of inflammation. The strict activation dependence of CD137 expression and its restricted expression on activated T cells, NK cells, and vascular endothelial cells at inflammatory sites make CD137 an ideally suited signal for the induction of monocyte-derived inflammatory DCs in vivo. These findings and their potency encouraged a phase I clinical trial of CD137L-DCs against Epstein-Barr virus-associated nasopharyngeal carcinoma. In this review, we introduce and summarize the history, the characteristics, and the transcriptional profile of CD137L-DC, and discuss the potential development and applications of CD137L-DC.

journal_name

Front Immunol

journal_title

Frontiers in immunology

authors

Zeng Q,Zhou Y,Schwarz H

doi

10.3389/fimmu.2019.02216

subject

Has Abstract

pub_date

2019-10-02 00:00:00

pages

2216

issn

1664-3224

journal_volume

10

pub_type

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