TIGIT Affects CAR NK-cell Effector Function in the Solid Tumor Microenvironment by Modulating Immune Synapse Strength.

ABSTRACT: Therapies using NK cells that express chimeric antigen receptors (CAR-NK) have been successfully employed against hematologic malignancies. However, solid tumors resist CAR-NKs partly by enriching tumor microenvironments with ligands for NK cell inhibitory receptors. Although the NK inhibitory receptor T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) has been implicated in impaired antitumor activity of endogenous NK cells, the consequences of TIGIT expression on engineered CAR-NKs have not been explored. To address this gap, we compared TIGIT-expressing and TIGIT-deleted human CAR-NKs targeting the GD2 solid tumor antigen in tumor immune microenvironment co-cultures and in vivo tumor immune microenvironment xenografts designed to

SUBMITTER: Navin I 

PROVIDER: S-EPMC12453546 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature