Wnt3a/β-Catenin Signaling Conditions Differentiation of Partially Exhausted T-effector Cells in Human Cancers

Cancer Immunology Research
Valeria SchinzariVincenzo Barnaba

Abstract

In this study, we investigated the role of the Wnt/β-catenin signaling pathway in antitumor immune responses. We report that the concentration of secreted Wnt3a was significantly higher in conditioned medium from tumor or nontumor tissues obtained from all hepatocellular carcinoma or colorectal cancer patients tested, than in serum of healthy donors or patients. In addition, both Wnt3a and β-catenin were overexpressed by tumor-infiltrating and nontumor-infiltrating CD4+ or CD8+ T cells. The majority of these T cells expressed a dysfunctional effector memory Eomes+T-bet-phenotype that we defined as partially exhausted, because they performed effector functions (in terms of interferon-γ and tumor necrosis factor-α production, as well as CD107a mobilization) despite their PD-1 expression. Wnt3a/β-catenin signaling in T naïve cells in vitro recapitulated the T-cell setting in vivo Indeed, the differentiation of cultured T naïve cells was arrested, producing cells that resembled the EomeshighT-betlowβ-cateninhigh T cells with moderate effector functions that infiltrated tumor and nontumor areas. Wnt3a blockade improved the capacity of T naïve cells to differentiate into effector cells in vitro However, Wnt3a blockade did not affect ...Continue Reading

References

Jul 1, 1997·The EMBO Journal·H AberleR Kemler
Oct 7, 2003·Nature Medicine·Valerie RubioPeter P Lee
Jul 12, 2008·Nature Reviews. Immunology·Frank J T StaalMachteld M Tiemessen
Jan 16, 2009·Proceedings of the National Academy of Sciences of the United States of America·Andy J ChienRandall T Moon
Jun 16, 2009·Nature Medicine·Luca GattinoniNicholas P Restifo
Sep 9, 2009·Development·Renée van Amerongen, Roel Nusse
Dec 23, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Dong-Mei ZhaoHai-Hui Xue
Feb 25, 2010·Annals of Surgical Oncology·Stephen B Edge, Carolyn C Compton
May 12, 2010·Proceedings of the National Academy of Sciences of the United States of America·Grégoire JeannetWerner Held
Aug 7, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Luca GattinoniNicholas P Restifo
Dec 15, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Gregory DriessensThomas F Gajewski
Sep 20, 2011·Nature Medicine·Luca GattinoniNicholas P Restifo
Apr 3, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Eui Ho KimM Suresh
Jun 12, 2012·Cell·Hans Clevers, Roel Nusse
Jul 21, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Tomonori YaguchiYutaka Kawakami
Dec 22, 2012·Nature Reviews. Cancer·Jamie N Anastas, Randall T Moon
May 17, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Cecilia OderupEugene C Butcher
Sep 12, 2013·Nature Reviews. Genetics·Ian R WatsonLynda Chin
Oct 29, 2013·Nature Communications·Oksana VoloshanenkoMichael Boutros
Apr 8, 2014·Nature Immunology·Emily B HeikampJonathan D Powell
Nov 20, 2014·The New England Journal of Medicine·Alexandra SnyderTimothy A Chan
Mar 3, 2015·Proceedings of the National Academy of Sciences of the United States of America·Chunmei FuAimin Jiang
Apr 4, 2015·Science·Padmanee Sharma, James P Allison
Apr 4, 2015·Science·Ton N Schumacher, Robert D Schreiber
Apr 22, 2015·The New England Journal of Medicine·Michael A PostowF Stephen Hodi
May 15, 2015·Nature·Stefani SprangerThomas F Gajewski
Jul 25, 2015·Nature Reviews. Immunology·E John Wherry, Makoto Kurachi
Sep 18, 2015·Journal for Immunotherapy of Cancer·Stefani Spranger, Thomas F Gajewski
Apr 15, 2016·World Journal of Gastroenterology : WJG·Liu-Hong PanDeng-Fu Yao
May 4, 2016·Oncoimmunology·Stefani Spranger, Thomas F Gajewski
Nov 14, 2016·Stem Cell Research·Iris AugustinMichael Boutros
Aug 16, 2017·Oncoimmunology·Eleonora TimperiVincenzo Barnaba

❮ Previous
Next ❯

Citations

May 22, 2019·Journal of Cellular and Molecular Medicine·Qiancheng JingYong Liu
Mar 7, 2020·Frontiers in Immunology·Amol SuryawanshiSanthakumar Manicassamy
Jun 3, 2020·International Journal of Cancer. Journal International Du Cancer·Daniela GalleranoEleonora Timperi
Sep 15, 2020·Frontiers in Oncology·Xiaobo NieWei-Dong Chen
Jul 19, 2018·Cancer Immunology Research·Ilenia PacellaSilvia Piconese
Feb 18, 2020·Biochemical and Biophysical Research Communications·Yanmei ZhangWei Xu
Oct 12, 2021·Expert Opinion on Therapeutic Targets·Michael Kahn

❮ Previous
Next ❯

Related Concepts

Related Feeds

Carcinoma, Hepatocellular

Hepatocellular Carcinoma is a malignant cancer in liver epithelial cells. Discover the latest research on Hepatocellular Carcinoma here.

CD4/CD8 Signaling

Cluster of differentiation 4 and 8 (CD8 and CD8) are glycoproteins founds on the surface of immune cells. Here is the latest research on their role in cell signaling pathways.

Adherens Junctions

An adherens junction is defined as a cell junction whose cytoplasmic face is linked to the actin cytoskeleton. They can appear as bands encircling the cell (zonula adherens) or as spots of attachment to the extracellular matrix (adhesion plaques). Adherens junctions uniquely disassemble in uterine epithelial cells to allow the blastocyst to penetrate between epithelial cells. Discover the latest research on adherens junctions here.

Cadherins and Catenins

Cadherins (named for "calcium-dependent adhesion") are a type of cell adhesion molecule (CAM) that is important in the formation of adherens junctions to bind cells with each other. Catenins are a family of proteins found in complexes with cadherin cell adhesion molecules of animal cells: alpha-catenin can bind to β-catenin and can also bind actin. β-catenin binds the cytoplasmic domain of some cadherins. Discover the latest research on cadherins and catenins here.