RT Journal Article
SR Electronic
T1 Gene of the month: T-cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT)
JF Journal of Clinical Pathology
JO J Clin Pathol
FD BMJ Publishing Group Ltd and Association of Clinical Pathologists
SP 217
OP 221
DO 10.1136/jclinpath-2021-207789
VO 75
IS 4
A1 Louisa Bolm
A1 Natalie Petruch
A1 Shivan Sivakumar
A1 Nicola E Annels
A1 Adam Enver Frampton
YR 2022
UL http://jcp.bmj.com/content/75/4/217.abstract
AB Immune modulators play a crucial role in carcinogenesis and cancer progression by impairing cancer cell-targeted immune responses. T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) regulates T-cell function and cancer cell recognition and was therefore identified as a promising target for cancer immunotherapy. TIGIT is expressed in T cells and natural killer (NK) cells and has three ligands: CD155, CD112 and CD113. CD155 binds TIGIT with the highest affinity and promotes direct and indirect downregulation of T-cell response. TIGIT signalling further inhibits NK function and secretion of proinflammatory cytokines. An association between TIGIT expression and poor survival was identified in multiple cancer entities. Blocking TIGIT with monoclonal antibodies, and a combination of TIGIT and programmed cell death protein 1 blockade in particular, prevented tumour progression, distant metastasis and tumour recurrence in in vivo models. Inhibition of TIGIT is currently evaluated in first clinical trials.