Anti-TIGIT (Hu) from Mouse (Clone TG1)
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Clone TG1 is the first monoclonal antibody detecting TIGIT (T cell immunoreceptor with Ig and ITIM domains) in routine formalin-fixed paraffin-embedded 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.
TIGIT (T-cell immunoreceptor with Ig and ITIM domains) is a member of the poliovirus receptor (PVR) family and acts as an im-mune checkpoint protein expressed on subsets of T lymphocytes. The expression of TIGIT has been reported on NK cells, regu-latory T cells, follicular T helper cells, memory CD4+ T cells, and CD8+ T cells, but it is not expressed on B cells or naive CD4+ T cells. TIGIT may be upregulated on naive CD4+ T cells upon activation. TIGIT has been shown to be upregulated on T cells in multiple cancer models. The ligands CD155 and CD112 are also highly expressed on dendritic cells and macrophages in several types of cancer. Additionally, TIGIT expression is highly correlated with the expression of other coinhibitory molecules, including PD-1. In addition to directly inhibiting cytotoxic T-cell activity, TIGIT can foster an immunosuppressive microenvironment through its impact on other immune cells, for example, by binding to CD155 on the surface of dendritic cells or by manipulating NK cell activity. TIGIT inhibiting drugs are currently being developed. 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.
Immunohistochemistry of human TG1 in routine formalin-fixed paraffin-embedded tissue samples
A: Normal human tonsil with numerous TIGIT-positive lymphocytes
B: Tumor infiltrating lymphocytes in colorectal carcinoma
C: Inflamatory lymphoid infiltrate in Hashimoto thyroiditis
D: Sarcoid granuloma interspersed with TIGIT-positive lymphocytes
B) Colorectal carcinoma
(C) Hashimoto thyreoiditis
(D) Sarcoid granuloma
(pictures courtesy of Prof. Guido Sauter, Department of Pathology, University Hospital Eppendorf, Hamburg, Germany)
Western blot performed with DIA-TG1 (1:500) on recombinant human TIGIT.
References for clone TG1
- Blessin NC et al. Patterns of TIGIT expression in normal lymphatic tissue, inflammation and cancer. Disease Markers, Volume 2019, Article ID 5160565, 13 pages, https://doi.org/10.1155/2019/5160565
- Li W et al. Expression of the immune checkpoint receptor TIGIT in Hodgkin’s lymphoma. BMC Cancer 2018, 18:1209, https://doi.org/10.1186/s12885-018-5111-1
- Blessin NC et al. Abstract 696: Patterns of TIGIT expression in normal lymphatic tissue, inflammation and cancer. Pro-ceedings: AACR Annual Meeting 2018; April 14-18, 2018; Chicago, IL., DOI: 10.1158/1538-7445.AM2018-696, July 2018
- Simon R et al. Abstract 2142: High variability of TIGIT expression in Hodgkin’s lymphoma. Proceedings: AACR Annual Meeting 2018; April 14-18, 2018; Chicago, IL, DOI: 10.1158/1538-7445.AM2018-2142 Published July 2018
- Blake SJ et al. Molecular pathways: targeting CD96 and TIGIT for cancer immunotherapy. Clin Cancer Res. 2016; 22(21): 5183-5188. doi:10.1158/1078-0432.CCR-16-0933.
- Grogan J et al. The immunoreceptor TIGIT regulates anti-tumor immunity. J Immunother Cancer. 2016:4(suppl 1):P209.
- Kurtulus S et al. TIGIT predominantly regulates the immune response via regulatory T cells. J Clin Invest. 2015; 125(11): 4053- 4062. doi:10.1172/JCI81187
- Lozano E et al. The TIGIT/CD226 axis regulates human T cell function. J Immunol. 2012;188(8):3869-3875. doi:10.4049/jimmunol.1103627
- Pauken KE, Wherry EJ. TIGIT and CD226: tipping the balance between co stimulatory and coinhibitory molecules to augment the cancer immunotherapy toolkit. Cancer Cell. 2014;26(6):785-787. doi:10.1016/j.ccell.2014.11.016.
- Stanietsky N et al. The interaction of TIGIT with PVR and PVRL2 inhibits human NK cell cytotoxicity. Proc Natl Acad Sci U S A. 2009;106(42): 17858-17863. doi:10.1073/pnas.0903474106