Human CD1c(+) DCs are critical cellular mediators of immune responses induced by immunogenic cell death
Publication year
2016Author(s)
Number of pages
15 p.
Source
Oncoimmunology, 5, 8, (2016), pp. 1-15, article e1192739ISSN
Publication type
Article / Letter to editor
Display more detailsDisplay less details
Organization
Tumorimmunology
CMBI
Medical Oncology
Journal title
Oncoimmunology
Volume
vol. 5
Issue
iss. 8
Languages used
English (eng)
Page start
p. 1
Page end
p. 15
Subject
Radboudumc 2: Cancer development and immune defence RIMLS: Radboud Institute for Molecular Life SciencesAbstract
Chemotherapeutics, including the platinum compounds oxaliplatin (OXP) and cisplatin (CDDP), are standard care of treatment for cancer. Although chemotherapy has long been considered immunosuppressive, evidence now suggests that certain cytotoxic agents can efficiently stimulate antitumor responses, through the induction of a form of apoptosis, called immunogenic cell death (ICD). ICD is characterized by exposure of calreticulin and heat shock proteins (HSPs), secretion of ATP and release of high-mobility group box 1 (HMGB1). Proper activation of the immune system relies on the integration of these signals by dendritic cells (DCs). Studies on the crucial role of DCs, in the context of ICD, have been performed using mouse models or human in vitro-generated monocyte-derived DCs (moDCs), which do not fully recapitulate the in vivo situation. Here, we explore the effect of platinum-induced ICD on phenotype and function of human blood circulating DCs. Tumor cells were treated with OXP or CDDP and induction of ICD was investigated. We show that both platinum drugs triggered translocation of calreticulin and HSP70, as well as the release of ATP and HMGB1. Platinum treatment increased phagocytosis of tumor fragments by human blood DCs and enhanced phenotypic maturation of blood myeloid and plasmacytoid DCs. Moreover, upon interaction with platinum-treated tumor cells, CD1c(+) DCs efficiently stimulated allogeneic proliferation of T lymphocytes. Together, our observations indicate that platinum-treated tumor cells may exert an active stimulatory effect on human blood DCs. In particular, these data suggest that CD1c(+) DCs are critical mediators of immune responses induced by ICD.
This item appears in the following Collection(s)
- Academic publications [246764]
- Electronic publications [134215]
- Faculty of Medical Sciences [93461]
- Open Access publications [107738]
Upload full text
Use your RU credentials (u/z-number and password) to log in with SURFconext to upload a file for processing by the repository team.