TLR9 Mediated Tumor-Stroma Interactions in Human Papilloma Virus (HPV)-Positive Head and Neck Squamous Cell Carcinoma Up-Regulate PD-L1 and PD-L2
Identifieur interne : 000404 ( Main/Merge ); précédent : 000403; suivant : 000405TLR9 Mediated Tumor-Stroma Interactions in Human Papilloma Virus (HPV)-Positive Head and Neck Squamous Cell Carcinoma Up-Regulate PD-L1 and PD-L2
Auteurs : Paramita Baruah [Royaume-Uni] ; Jessica Bullenkamp [Royaume-Uni] ; Philip O. G. Wilson [Royaume-Uni] ; Michael Lee [Royaume-Uni] ; Juan Carlos Kaski [Royaume-Uni] ; Ingrid E. Dumitriu [Royaume-Uni]Source :
- Frontiers in Immunology [ 1664-3224 ] ; 2019.
Abstract
Url:
DOI: 10.3389/fimmu.2019.01644
PubMed: 31379843
PubMed Central: 6648892
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PMC:6648892Le document en format XML
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<author><name sortKey="Dumitriu, Ingrid E" sort="Dumitriu, Ingrid E" uniqKey="Dumitriu I" first="Ingrid E." last="Dumitriu">Ingrid E. Dumitriu</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">TLR9 Mediated Tumor-Stroma Interactions in Human Papilloma Virus (HPV)-Positive Head and Neck Squamous Cell Carcinoma Up-Regulate PD-L1 and PD-L2</title>
<author><name sortKey="Baruah, Paramita" sort="Baruah, Paramita" uniqKey="Baruah P" first="Paramita" last="Baruah">Paramita Baruah</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Department of Ears, Nose and Throat (ENT), St. George's University Hospitals NHS Foundation Trust</institution>
,<addr-line>London</addr-line>
,<country>United Kingdom</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Molecular and Clinical Sciences Research Institute and Cardiology Clinical Academic Group, St. George's, University of London</institution>
,<addr-line>London</addr-line>
,<country>United Kingdom</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Bullenkamp, Jessica" sort="Bullenkamp, Jessica" uniqKey="Bullenkamp J" first="Jessica" last="Bullenkamp">Jessica Bullenkamp</name>
<affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Molecular and Clinical Sciences Research Institute and Cardiology Clinical Academic Group, St. George's, University of London</institution>
,<addr-line>London</addr-line>
,<country>United Kingdom</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Wilson, Philip O G" sort="Wilson, Philip O G" uniqKey="Wilson P" first="Philip O. G." last="Wilson">Philip O. G. Wilson</name>
<affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Department of Pathology, St. George's University Hospitals NHS Foundation Trust</institution>
,<addr-line>London</addr-line>
,<country>United Kingdom</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Lee, Michael" sort="Lee, Michael" uniqKey="Lee M" first="Michael" last="Lee">Michael Lee</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Department of Ears, Nose and Throat (ENT), St. George's University Hospitals NHS Foundation Trust</institution>
,<addr-line>London</addr-line>
,<country>United Kingdom</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Kaski, Juan Carlos" sort="Kaski, Juan Carlos" uniqKey="Kaski J" first="Juan Carlos" last="Kaski">Juan Carlos Kaski</name>
<affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Molecular and Clinical Sciences Research Institute and Cardiology Clinical Academic Group, St. George's, University of London</institution>
,<addr-line>London</addr-line>
,<country>United Kingdom</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Dumitriu, Ingrid E" sort="Dumitriu, Ingrid E" uniqKey="Dumitriu I" first="Ingrid E." last="Dumitriu">Ingrid E. Dumitriu</name>
<affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Molecular and Clinical Sciences Research Institute and Cardiology Clinical Academic Group, St. George's, University of London</institution>
,<addr-line>London</addr-line>
,<country>United Kingdom</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
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</analytic>
<series><title level="j">Frontiers in Immunology</title>
<idno type="eISSN">1664-3224</idno>
<imprint><date when="2019">2019</date>
</imprint>
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<front><div type="abstract" xml:lang="en"><p><bold>Background:</bold>
The co-inhibitory receptor PD-1 is expressed in many tumors including head and neck squamous cell carcinoma (HNSCC) and is an important immunotherapy target. However, the role of PD-1 ligands, PD-L1, and particularly PD-L2, in the tumor-stromal cell interactions that cause a tumor-permissive environment in HNSCC is not completely understood and is the focus of our study.</p>
<p><bold>Methods:</bold>
Expression of PD-L1 and PD-L2 was analyzed by immunohistochemistry <italic>in situ</italic>
in HNSCC tumor tissue. Co-cultures were established between stromal cells (fibroblasts and macrophages) and human papilloma virus (HPV)-positive and HPV-negative HNSCC cell lines (HNSCCs) and PD-1 ligands expression was analyzed using flow cytometry.</p>
<p><bold>Results:</bold>
PD-L1 and PD-L2 were expressed both in tumor cells and stroma in HNSCC tissue <italic>in situ</italic>
. <italic>In vitro</italic>
, basal expression of PD-L1 and PD-L2 was low in HNSCCs and high on fibroblasts and macrophages. Interestingly, HPV-positive but not HPV-negative HNSCCs increased the expression of both PD-1 ligands on fibroblasts upon co-culture. This effect was not observed with macrophages. Conversely, both fibroblasts and macrophages increased PD-1 ligands on HPV-positive HNSCCs, whilst this was not observed in HPV-negative HNSCCs. Crucially, we demonstrate that up-regulation of PD-L1 and PD-L2 on fibroblasts by HPV-positive HNSCCs is mediated via TLR9.</p>
<p><bold>Conclusions:</bold>
This work demonstrates in an <italic>in vitro</italic>
model that HPV-positive HNSCCs regulate PD-L1/2 expression on fibroblasts via TLR9. This may open novel avenues to modulate immune checkpoint regulator PD-1 and its ligands by targeting TLR9.</p>
</div>
</front>
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