Pan-Cancer Analysis of TIGIT and Its Association with the Tumor Immune Microenvironment and Potential in Cold Tumor Therapy
DOI:
https://doi.org/10.54097/8wmxvg77Keywords:
TIGIT, Immune checkpoint inhibitors, Cold tumors, Tumor microenvironment.Abstract
T cell immunoreceptor with Ig and ITIM domains (TIGIT) is an inhibitory receptor that marks exhausted and inflamed immunity and offers a practical handle to restore anti-tumor function. This study synthesizes evidence across bulk transcriptomic resources, pathology series, and single cell datasets to define TIGIT expression, ligand geography, and clinical implications. TIGIT is concentrated in activated CD8+ and CD4+ T cells, regulatory T cells, and natural killer cells. Its ligands CD155 and CD112 are widely expressed by tumor and myeloid compartments. TIGIT tracks with immune and stromal signals and shows context dependent prognostic value across histologies. These features support strategies that restore the CD226 costimulatory axis and PD-1 or PD-L1 blockade with TIGIT inhibition in ligand rich niches. In immunologically cold or immune excluded tumors, low bulk TIGIT often reflects limited lymphocyte entry rather than absence of target. Therefore, a sequence remodel first and release second. Normalizing vasculature, easing stromal and chemokine barriers, or inducing type I and type III interferon tone can prime responses to dual checkpoint therapy. Where MHC class I loss shifts surveillance toward innate cells, TIGIT blockade should be combined with natural killer supportive approaches. Together these principles outline biomarker guided and tumor microenvironment aware deployment of TIGIT centered therapy.
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