cDC2 plasticity and acquisition of a DC3-like phenotype mediated by IL-6 and PGE2 in a patient-derived colorectal cancer organoids model.
3D model
CD14+ cDC2
Colorectal cancer
Conventional dendritic cells type 2
DC3
Dendritic cell dysfunction
IL‐6
Immunosuppression
Metastasis
PGE2
Patient‐derived organoids
Tumor microenvironment
Journal
European journal of immunology
ISSN: 1521-4141
Titre abrégé: Eur J Immunol
Pays: Germany
ID NLM: 1273201
Informations de publication
Date de publication:
21 Mar 2024
21 Mar 2024
Historique:
revised:
06
03
2024
received:
10
11
2023
accepted:
08
03
2024
medline:
21
3
2024
pubmed:
21
3
2024
entrez:
21
3
2024
Statut:
aheadofprint
Résumé
Metastatic colorectal cancer (CRC) is highly resistant to therapy and prone to recur. The tumor-induced local and systemic immunosuppression allows cancer cells to evade immunosurveillance, facilitating their proliferation and dissemination. Dendritic cells (DCs) are required for the detection, processing, and presentation of tumor antigens, and subsequently for the activation of antigen-specific T cells to orchestrate an effective antitumor response. Notably, successful tumors have evolved mechanisms to disrupt and impair DC functions, underlining the key role of tumor-induced DC dysfunction in promoting tumor growth, metastasis initiation, and treatment resistance. Conventional DC type 2 (cDC2) are highly prevalent in tumors and have been shown to present high phenotypic and functional plasticity in response to tumor-released environmental cues. This plasticity reverberates on both the development of antitumor responses and on the efficacy of immunotherapies in cancer patients. Uncovering the processes, mechanisms, and mediators by which CRC shapes and disrupts cDC2 functions is crucial to restoring their full antitumor potential. In this study, we use our recently developed 3D DC-tumor co-culture system to investigate how patient-derived primary and metastatic CRC organoids modulate cDC2 phenotype and function. We first demonstrate that our collagen-based system displays extensive interaction between cDC2 and tumor organoids. Interestingly, we show that tumor-corrupted cDC2 shift toward a CD14+ population with defective expression of maturation markers, an intermediate phenotype positioned between cDC2 and monocytes, and impaired T-cell activating abilities. This phenotype aligns with the newly defined DC3 (CD14
Identifiants
pubmed: 38509863
doi: 10.1002/eji.202350891
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2350891Subventions
Organisme : Radboudumc
Organisme : the Netherlands Organisation for Scientific Research
ID : 91719371
Organisme : IHSeed
ID : LSHM22042_SGF
Organisme : JO RUMC
Organisme : Health Holland
ID : LSHM18056-SGF
Informations de copyright
© 2024 The Authors. European Journal of Immunology published by Wiley‐VCH GmbH.
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