The cytokine milieu compromises functional capacity of tumor-infiltrating plasmacytoid dendritic cells in HPV-negative but not in HPV-positive HNSCC.
Biomarkers
Case-Control Studies
Cell Transformation, Viral
Cytokines
/ metabolism
Dendritic Cells
/ immunology
Disease Susceptibility
Gene Expression
Humans
Interferon-alpha
/ immunology
Papillomavirus Infections
/ complications
Squamous Cell Carcinoma of Head and Neck
/ etiology
T-Lymphocyte Subsets
/ immunology
T-Lymphocytes, Regulatory
/ immunology
Tumor Microenvironment
/ immunology
Head and neck cancer
Human papillomavirus
Interferon alpha
Plasmacytoid dendritic cells
Journal
Cancer immunology, immunotherapy : CII
ISSN: 1432-0851
Titre abrégé: Cancer Immunol Immunother
Pays: Germany
ID NLM: 8605732
Informations de publication
Date de publication:
Sep 2021
Sep 2021
Historique:
received:
20
07
2020
accepted:
25
01
2021
pubmed:
12
2
2021
medline:
24
8
2021
entrez:
11
2
2021
Statut:
ppublish
Résumé
Plasmacytoid dendritic cells (pDCs) are the most potent type I interferon-producing cells and play an important role in antiviral immunity. Tumor-infiltrating pDCs were shown to be predominantly pro-tumorigenic, with reduced ability to produce interferon alpha (IFNα) and confirmed capacity to prime regulatory T cells (Tregs) by the ICOS/ICOS-L pathway. Because a significant number of HNSCCs are induced by human papillomaviruses and show markedly different immune profiles than non-virally induced tumors, we compared the phenotype and functional capacity of HNSCC-infiltrating pDCs to the HPV status of the tumor. We observed a reduced capacity of pDCs to produce IFNα upon toll-like receptor activation in HPV-negative samples and a rather uncompromised functionality in HPV-associated tumors. Additionally, supernatants from non-virally induced but not HPV-associated tumor cell suspensions significantly inhibited IFNα production by peripheral blood-derived pDCs. We identified IL-10 and TNFα as the soluble pDC-suppressive factors with the highest variability between HPV-negative and HPV-positive tumor-derived supernatants. Additionally, we observed a positive correlation of tumor-infiltrating pDCs with Tregs in HPV-negative samples but not in virally induced tumors. Overall, our study indicates that the immunosuppressive cytokine milieu rich in IL-10 and TNFα in HPV-negative but not in HPV-positive HNSCC significantly affects the functional capacity of tumor-infiltrating pDCs, and such dysfunctional pDCs may further support the immunosuppressive tumor microenvironment by promoting the expansion of Tregs in the tumor tissue.
Identifiants
pubmed: 33569630
doi: 10.1007/s00262-021-02874-y
pii: 10.1007/s00262-021-02874-y
doi:
Substances chimiques
Biomarkers
0
Cytokines
0
Interferon-alpha
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2545-2557Subventions
Organisme : Grantová Agentura, Univerzita Karlova
ID : 668217
Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.
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