TMIGD2 protein can be detected in cells of epithelial and endothelial origins, and is able to enhance angiogenesis in vitro when overexpressed by endothelial cell lines. Furthermore, TMIGD2 is reported as a stimulatory receptor expressed primarily on naive T cells. Like other CD28 family members, TMIGD2 is an Ig superfamily member with an extracellular IgV-like domain, a transmembrane region, and a cytoplasmic tail. The cytoplasmic tail contains tyrosine residues which can be phosphorylated 2 and a proline-rich domain which associates with multiple Src homology 3 (SH3)-containing signaling molecules. Together, these studies suggest that TMIGD2 has multiple functions depending on the cell type and signaling pathways. In summary, we have shown that the TMIGD2 pathway could represents a novel immunosuppressive mechanism within the tumor microenvironment and is an attractive target for human cancer therapy.
Xiao Y, Freeman GJ. A new B7:CD28 family checkpoint target for cancer immunotherapy: HHLA2. Clinical cancer research?: an official journal of the American Association for Cancer Research. 2015;21(10):2201-2203.