Immunomodulatory role of Keratin 76 in oral and gastric cancer.

Nature Communications
Inês SequeiraFiona M Watt

Abstract

Keratin 76 (Krt76) is expressed in the differentiated epithelial layers of skin, oral cavity and squamous stomach. Krt76 downregulation in human oral squamous cell carcinomas (OSCC) correlates with poor prognosis. We show that genetic ablation of Krt76 in mice leads to spleen and lymph node enlargement, an increase in regulatory T cells (Tregs) and high levels of pro-inflammatory cytokines. Krt76-/- Tregs have increased suppressive ability correlated with increased CD39 and CD73 expression, while their effector T cells are less proliferative than controls. Loss of Krt76 increases carcinogen-induced tumours in tongue and squamous stomach. Carcinogenesis is further increased when Treg levels are elevated experimentally. The carcinogenesis response includes upregulation of pro-inflammatory cytokines and enhanced accumulation of Tregs in the tumour microenvironment. Tregs also accumulate in human OSCC exhibiting Krt76 loss. Our study highlights the role of epithelial cells in modulating carcinogenesis via communication with cells of the immune system.

References

Mar 2, 1999·The Journal of Experimental Medicine·R E ToesC J Melief
Mar 22, 2001·EMBO Reports·M CokolB Rost
Jan 22, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Xiao-Han TangLorraine J Gudas
Mar 25, 2006·Nature Reviews. Immunology·Weiping Zou
Jul 25, 2006·Blood·Marc Beyer, Joachim L Schultze
May 16, 2007·The Journal of Experimental Medicine·Silvia DeaglioSimon C Robson
Aug 3, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Laura StraussTheresa L Whiteside
Nov 21, 2007·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Robert ZeiserRobert S Negrin
May 8, 2008·Histochemistry and Cell Biology·Roland MollLutz Langbein
Mar 17, 2009·Autoimmunity Reviews·Miriam WittmannJulius Renne
Mar 24, 2009·Annual Review of Immunology·Charles A Dinarello
Apr 11, 2009·Trends in Immunology·Guttorm HaraldsenAxel M Küchler
Oct 15, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Magis MandapathilTheresa L Whiteside
May 26, 2010·Oncogene·F MartinF Ghiringhelli
Nov 26, 2010·The Journal of Clinical Investigation·Yenkel Grinberg-BleyerBenoît L Salomon
Dec 17, 2010·Nature Reviews. Cancer·C René LeemansRuud H Brakenhoff
Feb 3, 2011·Methods in Molecular Biology·Katharina Lahl, Tim Sparwasser
Jun 8, 2011·International Journal of Biological Sciences·Brian F Zamarron, WanJun Chen
Jun 30, 2012·Nature Methods·Fabrice de ChaumontJean-Christophe Olivo-Marin
Feb 5, 2013·Journal of Cell Science·Ryan P HobbsPierre A Coulombe
Nov 13, 2013·Proceedings of the National Academy of Sciences of the United States of America·Juliane C LessardPierre A Coulombe
Nov 28, 2013·Methods in Molecular Biology·Inês SequeiraJean-François Nicolas
Apr 12, 2014·Nature Communications·Kifayathullah Liakath-AliFiona M Watt
Apr 23, 2014·The Journal of Investigative Dermatology·Heinz FischerLeopold Eckhart
Jul 22, 2014·Nature·Chris SchieringFiona Powrie
Jan 13, 2015·Nature Communications·Esther HosteFiona M Watt
Apr 17, 2016·Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology·Sai LiuQianming Chen
Aug 10, 2016·Developmental Cell·Ryan P HobbsPierre A Coulombe
Oct 21, 2016·Cancer Immunology, Immunotherapy : CII·Kentaro MikiYasuharu Sato
Nov 3, 2016·Cold Spring Harbor Perspectives in Biology·Harald Herrmann, Ueli Aebi

❮ Previous
Next ❯

Citations

Jun 18, 2019·Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology·Shan WangYumei Niu
Apr 27, 2019·Frontiers in Cell and Developmental Biology·Madison CanningYan Cui
Oct 4, 2020·Science Advances·Clara Louise HedegaardAlvaro Mata
Oct 23, 2020·International Journal of Cancer. Journal International Du Cancer·Zihang LingXiaoan Tao
Aug 13, 2021·Frontiers in Cell and Developmental Biology·Diana Pereira, Inês Sequeira
Nov 25, 2021·Experimental and Therapeutic Medicine·Xin Li, Weidong Yang

❮ Previous
Next ❯

Methods Mentioned

BETA
flow cytometry
PCR

Software Mentioned

GraphPad
FlowJo
ICY
ICY software
Prism7
NanoZoomer
Prism
Graph Pad

Related Concepts

Related Feeds

Carcinoma, Squamous Cell

Basal cell carcinoma is a form of malignant skin cancer found on the head and neck regions and has low rates of metastasis. Discover the latest research on basal cell carcinoma here.

Related Papers

Clinical Immunology : the Official Journal of the Clinical Immunology Society
Chindu GovindarajMagdalena Plebanski
Journal of Cellular and Molecular Medicine
Yi WangXizhong Shen
Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology
Stephan SchwarzOliver Driemel
© 2022 Meta ULC. All rights reserved