A growing number of immune checkpoints emerge as targets for anticancer therapy. Cancer cells and the cells of the surrounding microenvironment have been shown to upregulate the expression of components to suppress the antitumor immune response by generating coinhibitory signals. So far, PD-1 and CTLA-4 emerged as the most successful immune targets for anticancer therapies. The recently discovered TIGIT pathway provides significant therapeutic promise, particularly in combination with other immune checkpoint inhibitors. Dianova’s antibody development program concentrates on monoclonal antibodies against immune checkpoint targets for immunohistochemical application in standard FFPE human tumor tissues for diagnostic purposes.
Immunohistochemistry of human TIGIT in formalin-fixed paraffin-embedded tissue sections
Clone TG1 is the first monoclonal antibody detecting TIGIT in standard FFPE human tissue specimen. It has been validated for the identification of TIGIT positive T-cells infiltrating human tumors in order to allow the detection of TIGIT in the tumor microenvironment under pathological conditions. Immunohistochemical application of monoclonal antibody TG1 may provide valuable information for clinical research and potential therapeutic interventions specifically targeting the TIGIT-related tumor immunology checkpoint.
Normal human tonsil with numerous TIGIT-positive lymphocytes
Tumor infiltrating lymphocytes in colorectal carcinoma
Inflammatory lymphoid infiltrate in Hashimoto thyreoiditis
Sarcoid granuloma interspersed with TIGIT-positive lymphocytes
Strong membrane staining of TIGIT-positive lymphocytes in human FFPE tissues with the monoclonal antibody TG1.
Each image is shown at 20x magnification. Sections were stained for TIGIT antibody using a HRP conjugated polymer system with DAB as a chromogen (brown) and counterstained with haematoxylin (blue).
(pictures courtesy of Dr. med. Andrea Hinsch and Niclas Blessin, Institute of Pathology, University Hospital Eppendorf (UKE), Hamburg, Germany)
The immunoreceptor TIGIT acts as an inhibitory immune checkpoint on both T cells and natural killer (NK) cells by a highly complexe pathway. Known ligands for TIGIT include CD155, and CD112. The TIGIT/CD155/CD112 network also interacts with other checkpoint regulators (see scheme above).
TIGIT expression on lymphocytes is highly correlated with the expression of other coinhibitory molecules, including PD-1. The complexities of the TIGIT pathway upregulated in inflammation and in cancer tumor and its interactions with other inhibitory checkpoint pathways offers opportunities for research and clinical translation.
We believe that monoclonal antibodies for reliable and standardized histopathological detection of immune checkpoint targets in tumor tissues will be crucial and indispensable for future studies and diagnostic approaches.
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