Pro-inflammatory allogeneic DCs promote activation of bystander immune cells and thereby license antigen-specific T-cell responses

Accumulating evidence support an important role for endogenous bystander dendritic cells (DCs) in the efficiency of autologous patient-derived DC-vaccines, as bystander DCs take up material from vaccine-DCs, migrate to draining lymph node and initiate antitumor T-cell responses. We examined the poss...

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Main Authors: Grammatiki Fotaki, Chuan Jin, Mohanraj Ramachandran, Iliana Kyriaki Kerzeli, Alex Karlsson-Parra, Di Yu, Magnus Essand
Format: Article
Language:English
Published: Taylor & Francis Group 2018-03-01
Series:OncoImmunology
Subjects:
Online Access:http://dx.doi.org/10.1080/2162402X.2017.1395126
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author Grammatiki Fotaki
Chuan Jin
Mohanraj Ramachandran
Iliana Kyriaki Kerzeli
Alex Karlsson-Parra
Di Yu
Magnus Essand
author_facet Grammatiki Fotaki
Chuan Jin
Mohanraj Ramachandran
Iliana Kyriaki Kerzeli
Alex Karlsson-Parra
Di Yu
Magnus Essand
author_sort Grammatiki Fotaki
collection DOAJ
description Accumulating evidence support an important role for endogenous bystander dendritic cells (DCs) in the efficiency of autologous patient-derived DC-vaccines, as bystander DCs take up material from vaccine-DCs, migrate to draining lymph node and initiate antitumor T-cell responses. We examined the possibility of using allogeneic DCs as vaccine-DCs to activate bystander immune cells and promote antigen-specific T-cell responses. We demonstrate that human DCs matured with polyI:C, R848 and IFN-γ (denoted COMBIG) in combination with an infection-enhanced adenovirus vector (denoted Ad5M) exhibit a pro-inflammatory state. COMBIG/Ad5M-matured allogeneic DCs (alloDCs) efficiently activated T-cells and NK-cells in allogeneic co-culture experiments. The secretion of immunostimulatory factors during the co-culture promoted the maturation of bystander-DCs, which efficiently cross-presented a model-antigen to activate antigen-specific CD8+ T-cells in vitro. We propose that alloDCs, in combination with Ad5M as loading vehicle, may be a cost-effective and logistically simplified DC vaccination strategy to induce anti-tumor immune responses in cancer patients.
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spelling doaj.art-757ca405ec724cd7902b3108800a9db22022-12-22T01:02:08ZengTaylor & Francis GroupOncoImmunology2162-402X2018-03-017310.1080/2162402X.2017.13951261395126Pro-inflammatory allogeneic DCs promote activation of bystander immune cells and thereby license antigen-specific T-cell responsesGrammatiki Fotaki0Chuan Jin1Mohanraj Ramachandran2Iliana Kyriaki Kerzeli3Alex Karlsson-Parra4Di Yu5Magnus Essand6Uppsala UniversityUppsala UniversityUppsala UniversityUppsala UniversityUppsala UniversityUppsala UniversityUppsala UniversityAccumulating evidence support an important role for endogenous bystander dendritic cells (DCs) in the efficiency of autologous patient-derived DC-vaccines, as bystander DCs take up material from vaccine-DCs, migrate to draining lymph node and initiate antitumor T-cell responses. We examined the possibility of using allogeneic DCs as vaccine-DCs to activate bystander immune cells and promote antigen-specific T-cell responses. We demonstrate that human DCs matured with polyI:C, R848 and IFN-γ (denoted COMBIG) in combination with an infection-enhanced adenovirus vector (denoted Ad5M) exhibit a pro-inflammatory state. COMBIG/Ad5M-matured allogeneic DCs (alloDCs) efficiently activated T-cells and NK-cells in allogeneic co-culture experiments. The secretion of immunostimulatory factors during the co-culture promoted the maturation of bystander-DCs, which efficiently cross-presented a model-antigen to activate antigen-specific CD8+ T-cells in vitro. We propose that alloDCs, in combination with Ad5M as loading vehicle, may be a cost-effective and logistically simplified DC vaccination strategy to induce anti-tumor immune responses in cancer patients.http://dx.doi.org/10.1080/2162402X.2017.1395126allogeneic dendritic cellscell-based immunotherapyinnate immune cellscell activation
spellingShingle Grammatiki Fotaki
Chuan Jin
Mohanraj Ramachandran
Iliana Kyriaki Kerzeli
Alex Karlsson-Parra
Di Yu
Magnus Essand
Pro-inflammatory allogeneic DCs promote activation of bystander immune cells and thereby license antigen-specific T-cell responses
OncoImmunology
allogeneic dendritic cells
cell-based immunotherapy
innate immune cells
cell activation
title Pro-inflammatory allogeneic DCs promote activation of bystander immune cells and thereby license antigen-specific T-cell responses
title_full Pro-inflammatory allogeneic DCs promote activation of bystander immune cells and thereby license antigen-specific T-cell responses
title_fullStr Pro-inflammatory allogeneic DCs promote activation of bystander immune cells and thereby license antigen-specific T-cell responses
title_full_unstemmed Pro-inflammatory allogeneic DCs promote activation of bystander immune cells and thereby license antigen-specific T-cell responses
title_short Pro-inflammatory allogeneic DCs promote activation of bystander immune cells and thereby license antigen-specific T-cell responses
title_sort pro inflammatory allogeneic dcs promote activation of bystander immune cells and thereby license antigen specific t cell responses
topic allogeneic dendritic cells
cell-based immunotherapy
innate immune cells
cell activation
url http://dx.doi.org/10.1080/2162402X.2017.1395126
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