TIGIT: Difference between revisions

'''TIGIT''' ({{IPAc-en|ˈ|t|ɪ|dʒ|ɪ|t}} {{Respell|TIJ|it}};<ref>{{cite web|url=https://www.youtube.com/watch?v=lgicCH6JGVk&t=811s|title=Lung Cancer and Immunotherapy with Dr. Patrick Forde and Oswald Peterson|work=YouTube|date=October 22, 2021|accessdate=5 July 2022}}</ref> also called '''T cell immunoreceptor with Ig and ITIM domains''') is an [[immune receptor]] present on some [[T cells]] and [[natural killer cell]]s (NK).<ref name="surface protein">{{cite journal | title=The surface protein TIGIT suppresses T cell activation by promoting the generation of mature immunoregulatory dendritic cells |vauthors=Yu X, Harden K, Gonzalez LC, Francesco M, Chiang E, Irving B, Tom I, Ivelja S, Refino CJ, Clark H, Eaton D, Grogan JL | journal=Nat Immunol |date=Jan 2009 | volume=10 | issue=1 | pages=48–57 | doi=10.1038/ni.1674 | pmid=19011627|s2cid=205361984 }}</ref> It is also identified as WUCAM<ref>{{cite journal | title=A novel molecular interaction for the adhesion of follicular CD4 T cells to follicular DC |vauthors=Boles KS, Vermi W, Facchetti F, Fuchs A, Wilson TJ, Diacovo TG, Cella M, Colonna M | journal=European Journal of Immunology |date=Mar 2009 | volume=39 | issue=3 | pages=695–703 | doi=10.1002/eji.200839116 | pmid=19197944 | pmc=3544471}}</ref> and Vstm3.<ref name="pmid21416464">{{cite journal | vauthors = Levin SD, Taft DW, Brandt CS, Bucher C, Howard ED, Chadwick EM, Johnston J, Hammond A, Bontadelli K, Ardourel D, Hebb L, Wolf A, Bukowski TR, Rixon MW, Kuijper JL, Ostrander CD, West JW, Bilsborough J, Fox B, Gao Z, Xu W, Ramsdell F, Blazar BR, Lewis KE|display-authors = 6 | title = Vstm3 is a member of the CD28 family and an important modulator of T-cell function | journal = European Journal of Immunology | volume = 41 | issue = 4 | pages = 902–15 | date = April 2011 | pmid = 21416464 | pmc = 3733993 | doi = 10.1002/eji.201041136 }}</ref> TIGIT could bind to [[CD155]] (PVR) on [[dendritic cells]] (DCs), [[macrophages]], etc. with high affinity, and also to [[CD112]] (PVRL2) with lower affinity.<ref name="surface protein"/>

Numerous clinical trials on TIGIT-blockade in cancer have recently been initiated, predominantly combination treatments. The first interim results show promise for combined TIGIT and [[PD-L1]] co-blockade in solid cancer patients.<ref>{{cite journal | vauthors = Ge Z, Peppelenbosch MP, Sprengers D, Kwekkeboom J | title = TIGIT, the Next Step Towards Successful Combination Immune Checkpoint Therapy in Cancer. | journal = Frontiers in Immunology | volume = 12 | pages = 699895 | date = 2021-07-22 | pmid = 34367161 | pmc = 8339559 | doi = 10.3389/fimmu.2021.699895 | doi-access = free }}</ref> MechanistallyMechanistically, research has shown that TIGIT-Fc fusion protein could interact with PVR on dendritic cells and increase its [[Interleukin 10|IL-10]] secretion level/decrease its [[Interleukin 12|IL-12]] secretion level under [[Lipopolysaccharide|LPS]] stimulation, and also inhibit T cell activation [[in vivo]].<ref name="surface protein"/>

During Human Immunodeficiency Virus ([[HIV]]) infection, TIGIT expressing CD8+ T cells hashave been shown to be expanded and associated with clinical markers of HIV disease progression in a diverse group of HIV infected individuals.<ref name="Marks Exhausted">{{cite journal | title=TIGIT Marks Exhausted T Cells, Correlates with Disease Progression, and Serves as a Target for Immune Restoration in HIV and SIV Infection | vauthors=Chew GM, Fujita T, Webb GM, Burwitz BJ, Wu HL, Reed JS, etal | journal=PLOS Pathogens | date=Jan 2016 |doi=10.1371/journal.ppat.1005349 | pmid= 26741490 | volume=12 | issue=1 | pmc=4704737 | pages=e1005349 | doi-access=free }}</ref> Elevated TIGIT levels remained sustained even among those with undetectable viral loads. and aA large fraction of HIV-specific CD8+ T cells simultaneously express both TIGIT and another negative checkpoint receptor, Programmed Death Protein 1 ([[PD-1]]) and retained several features of exhausted T cells.<ref name="Marks Exhausted"/> Blocking these pathways with novel targeted monoclonal antibodies synergistically rejuvenated HIV-specific CD8+ T cell responses.<ref name="Marks Exhausted"/> Further, the TIGIT pathway is active in the rhesus macaque non-human primate model, and mimics expression and function during Simian Immunodeficiency Virus (SIV) infection.<ref name="Marks Exhausted"/> This pathway can potentially be targeted to enhance killing of HIV infected cells during "Shock and Kill" HIV curative approaches.<ref name="shock and kill">{{cite journal | title=HIV: Shock and Kill | author=Steven G. Deeks | journal=Nature |date=July 2012 | volume=487 | issue=1 | pages=439–440 | doi=10.1038/487439a | pmid= 22836995| bibcode=2012Natur.487..439D | s2cid=205073070 }}</ref>

TIGIT and [[PD-1]] has been shown to be over -expressed on tumor antigen-specific (TA-specific) CD8+ T cells and CD8+ [[tumor infiltrating lymphocyte]]s (TILs) from individuals with melanoma.<ref name="chauvin">{{cite journal | title= TIGIT and PD-1 impair tumor antigen-specific CD8⁺ T cells in melanoma patients |author1=Joe-Marc Chauvin |author2=Ornella Pagliano |author3=Julien Fourcade |author4=Zhaojun Sun |author5=Hong Wang |author6=Cindy Sander |author7=John M. Kirkwood |author8=Tseng-hui Timothy Chen |author9=Mark Maurer |author10=Alan J. Korman |author11=Hassane M. Zarour |name-list-style=amp | journal=J Clin Invest |date=April 2015 | volume=125 | issue = 5 | pages=2046–2058 | doi=10.1172/JCI80445 | pmid= 25866972 | pmc=4463210}}</ref> Blockade of TIGIT and [[PD-1]] led to increased cell proliferation, cytokine production, and degranulation of TA-specific CD8+ T cells and TIL CD8+ T cells.<ref name="chauvin"/> It can be considered an [[immune checkpoint]].<ref name=TIGIT-2017>[http://www.onclive.com/publications/oncology-live/2017/vol-18-no-03/pharmaceutical-leaders-highlight-promise-of-tigit Pharmaceutical Leaders Highlight Promise of TIGIT. Feb 2017]</ref> Co-blockade of TIGIT and [[PD-1]] pathways elicits tumor rejection in preclinical murine models.<ref name="johnston">{{cite journal | title= The Immunoreceptor TIGIT Regulates Antitumor and Antiviral CD8+ T Cell Effector Function |author1=Robert J. Johnston |author2=Laetitia Comps-Agrar |author3=Jason Hackney |author4=Xin Yu |author5=Mahrukh Huseni |author6=Yagai Yang |author7=Summer Park |author8=Vincent Javinal |author9=Henry Chiu |author10=Bryan Irving |author11=Dan L. Eaton |author12=Jane L. Grogan | journal=Cancer Cell |date=December 2014 | volume=26 | issue=6 | pages=923–937 | doi=10.1016/j.ccell.2014.10.018 | pmid= 25465800 |doi-access=free }}</ref> Numerous anti-TIGIT therapies have entered clinical development.