CD226 and CD112/CD155 Pathway

Overview of CD226, CD112 and CD155

It has been known that the interaction between the NK-cell activating receptors and their ligands could modulate immune surveillance and affect tumor progression. The activating NK-cell receptor DNAX accessory molecule-1 (DNAM-1, CD226) contributes to tumor immune surveillance and plays a crucial role in NK cell-mediated recognition of several types of human tumors. The poliovirus receptor (PVR, CD155, NECL-5 TAGE4) and its family member poliovirus receptor-related 2 (PVRL2, CD112, NECTIN-2) are ligands for human and mouse CD226. Although human CD112 and CD155 are broadly distributed on epithelial and endothelial cells in many tissues, they are overexpressed on certain tumors.

Research of CD226 and CD112/CD155 Pathway

In vitro and in vivo studies have shown that CD226 triggers NK cell-mediated killing of tumor cells expressing CD155 and CD112. Meanwhile, downregulated CD112 and CD155 expression levels on viral-infected cells also impair the NK-cell cytotoxic activity to virus-infected cells. In several investigations, the function of CD266 as a costimulatory factor for the elimination of CD155 and CD112 expressing cancer cells by NK cells has been highlighted. The cytotoxic effects of NK cells mediated via CD266 against primary neuroblasts could be positively correlated to the expression intensity of CD155 on those cells. For the lysis of AML cells by NK cells, the expression of CD155 and CD112 is reported to be mandatory and blocking of CD266 reduces the cytotoxic capacity of NK cells in this model. Another study describes that CD155 is important for allogenic NK cell-mediated lysis of ovarian carcinoma cells. CD155 was shown to be a key ligand recognized by CD266 in NK cell-mediated suppression of metastases in a melanoma mouse model. Using the murine RMA lymphoma tumor model, CD155 and CD112 as ligands for CD266 stimulate the innate immune responses leading to cell-mediated tumor-specific immunity. Conversely, soluble CD266 has been proposed as a therapeutic option because the interaction of soluble CD266 with CD155 and CD112 inhibited cancer cell proliferation and reduced their metastatic potential in vitro.

Overview of CD226 and CD112/CD155 pathway. Fig.1 Overview of CD226 and CD112/CD155 pathway. (Solomon, 2018)

Services at Creative Biolabs

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  1. Solomon, B. L.; Garrido-Laguna, I. TIGIT: A novel immunotherapy target moving from bench to bedside. Cancer Immunol Immunother. 2018, 67(11): 1659-1667.

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