Gpa33, the Ig superfamily protein glycoprotein A33, has been implicated in immune dysregulation. It is expressed on fractions of B, dendritic, natural killer, and innate lymphoid cells, with prominent expression in the CD4+ T cell compartment. It may play a role in localization and/or preservation of an undifferentiated state in conventional CD4+ T cells [3].

In the context of Treg cells, GPA33 is expressed on a subset of human Treg cells. It is acquired late during tTreg cell development but not expressed on TGF-β-induced Treg cells. GPA33 can identify Treg cells in human blood that lack the ability to produce effector cytokines, and GPA33high Treg cells can be robustly and stably expanded in vitro, suggesting it can identify human tTreg cells for adoptive cell therapy [1].

In colorectal cancer, GPA33 is a promising surface antigen. Its expression shows intratumoral heterogeneity, and low levels are linked to tumor progression. WNT inhibition can induce its expression, and GPA33-targeted cellular therapy, such as CAR-T cells, can reduce xenograft growth [4]. Moreover, various therapeutic strategies targeting GPA33 in colorectal cancer have been developed, including pretargeted radioimmunotherapy, near-infrared photoimmunotherapy, and bispecific antibody-based therapies [2,5,6,7,8].

In summary, Gpa33 has significant implications in immune cell regulation, especially in identifying stable Treg cells. In colorectal cancer, it serves as an important target for various therapeutic approaches, and understanding its function and regulation through studies like those in the references can potentially lead to more effective treatment strategies for related diseases.