OX40+ plasmacytoid dendritic cells in the tumor microenvironment promote antitumor immunity

Plasmacytoid DCs (pDCs), the major producers of type I interferon, are principally recognized as key mediators of antiviral immunity. However, their role in tumor immunity is less clear. Depending on the context, pDCs can promote or suppress antitumor immune responses. In this study, we identified a...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of clinical investigation 2020-07, Vol.130 (7), p.3528-3542
Main Authors: Poropatich, Kate, Dominguez, Donye, Chan, Wen-Ching, Andrade, Jorge, Zha, Yuanyuan, Wray, Brian, Miska, Jason, Qin, Lei, Cole, Lisa, Coates, Sydney, Patel, Urjeet, Samant, Sandeep, Zhang, Bin
Format: Article
Language:English
Subjects:
Animals
Antigens
Antigens, Neoplasm - immunology
Antitumor activity
Biomedical research
CD8 antigen
CD8-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - pathology
Cell growth
Cell Line, Tumor
Dendritic cells
Dendritic Cells - immunology
Dendritic Cells - pathology
Eukaryotic Initiation Factor-2 - immunology
Female
Head & neck cancer
Humans
Immunity
Immunostimulation
Interferon
Ligands
Lymphatic system
Lymphocytes
Lymphocytes T
Male
Mice
Microscopy
Neoplasms, Experimental - immunology
Neoplasms, Experimental - pathology
Oxidative phosphorylation
Patients
Peptides
Phenotypes
Phosphorylation
Receptors, OX40 - immunology
Squamous cell carcinoma
Synergism
T cell receptors
Tumor Microenvironment - immunology
Tumor necrosis factor
Tumors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Plasmacytoid DCs (pDCs), the major producers of type I interferon, are principally recognized as key mediators of antiviral immunity. However, their role in tumor immunity is less clear. Depending on the context, pDCs can promote or suppress antitumor immune responses. In this study, we identified a naturally occurring pDC subset expressing high levels of OX40 (OX40+ pDC) enriched in the tumor microenvironment (TME) of head and neck squamous cell carcinoma. OX40+ pDCs were distinguished by a distinct immunostimulatory phenotype, cytolytic function, and ability to synergize with conventional DCs (cDCs) in generating potent tumor antigen-specific CD8+ T cell responses. Transcriptomically, we found that they selectively utilized EIF2 signaling and oxidative phosphorylation pathways. Moreover, depletion of pDCs in the murine OX40+ pDC-rich tumor model accelerated tumor growth. Collectively, we present evidence of a pDC subset in the TME that favors antitumor immunity.
ISSN:0021-9738
1558-8238
DOI:10.1172/JCI131992