TLR9 Mediated Tumor-Stroma Interactions in Human Papilloma Virus (HPV)-Positive Head and Neck Squamous Cell Carcinoma Up-Regulate PD-L1 and PD-L2

Frontiers in Immunology
Paramita BaruahIngrid E Dumitriu

Abstract

Background: 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. Methods: Expression of PD-L1 and PD-L2 was analyzed by immunohistochemistry in situ 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. Results: PD-L1 and PD-L2 were expressed both in tumor cells and stroma in HNSCC tissue in situ. In vitro, 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....Continue Reading

References

Oct 15, 1998·Proceedings of the National Academy of Sciences of the United States of America·A M KriegH L Davis
Jul 23, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ihsan GurselDennis M Klinman
Aug 7, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jun KonishiMasaharu Nishimura
Apr 20, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Michael R NazarethRichard B Bankert
May 27, 2008·Nature Reviews. Immunology·Weiping Zou, Lieping Chen
Feb 4, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Qiang GaoJia Fan
Jan 1, 2009·Journal of Innate Immunity·Alexandra K KiemerBruce L Zuraw
Jan 27, 2011·European Journal of Immunology·Sabine J WölfleKlaus Heeg
Mar 15, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Alenka KuznikRoman Jerala
Sep 16, 2011·Cancer Immunology, Immunotherapy : CII·Cailin Moira WilkeWeiping Zou
Jan 13, 2012·Current Opinion in Immunology·Suzanne L TopalianDrew M Pardoll
Jun 5, 2012·The New England Journal of Medicine·Julie R BrahmerJon M Wigginton
Feb 20, 2013·The Journal of Cell Biology·Graça Raposo, Willem Stoorvogel
Jun 4, 2013·The New England Journal of Medicine·Omid HamidAntoni Ribas
Jun 4, 2013·The New England Journal of Medicine·Jedd D WolchokMario Sznol
Aug 21, 2013·Trends in Immunology·Sabrina CeerazRandolph J Noelle
Aug 30, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·John J KaminskiKatherine A Fitzgerald
Sep 21, 2013·Nature·Melissa R Junttila, Frederic J de Sauvage
Nov 13, 2013·Laboratory Investigation; a Journal of Technical Methods and Pathology·Vamsidhar VelchetiDavid L Rimm
Mar 5, 2014·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Suzanne L TopalianF Stephen Hodi
Dec 9, 2014·The New England Journal of Medicine·Stephen M AnsellPhilippe Armand
Dec 24, 2014·Nature Reviews. Immunology·Linh T Nguyen, Pamela S Ohashi
Oct 31, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Sherene LoiJustin M Balko
Jun 10, 2016·Nature·Keisuke KataokaSeishi Ogawa
Sep 14, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Julie GeorgeTakashi Kohno
Jun 18, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jennifer H YearleyTerrill McClanahan
Sep 14, 2018·Frontiers in Oncology·Martin David Forster, Michael-John Devlin
Mar 21, 2019·Current Opinion in Oncology·Esma Saada-BouzidJoël Guigay

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Methods Mentioned

BETA
biopsies
density gradient centrifugation
flow cytometry
scraping
FCS
ELISA
biopsy
RNASeq
dissection

Software Mentioned

NDP
FlowJo
scan
GraphPad Prism

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