Cd3e, also known as CD3 epsilon, is a crucial component of the CD3 complex. This complex pairs with the Ag binding heterodimer (TCRαβ or TCRγδ) to form the complete αβ or γδ T cell receptor (TCR). The CD3 complex is essential for TCR signaling, which is vital for T cell activation, a key process in the immune response [2].

CD3E humanized mice, created by replacing specific exons of the mouse Cd3e gene with human counterparts, expressed only human CD3E. The proportion of lymphocytes in the thymus and spleen was not significantly different from wild-type mice. Pharmacodynamic studies in these mice showed that CD3E monoclonal antibody promoted tumor growth, potentially due to activation-induced cell death, while bispecific antibody blinatumomab inhibited tumor growth, indicating the value of this model for evaluating CD3E antibody drugs [1]. CD3e-immunotoxin treatment led to an enrichment of tissue-resident Foxp3+ Tregs, preferentially depleting CD3ehi T cells and reshaping organ-specific T-cell composition [3]. In muscle-invasive bladder cancer, high expression of CD3E was associated with better overall survival, more abundant CD8+ T cells and macrophage M1, higher expression of immune checkpoints, and a higher percentage of responders to immunotherapy [4]. In cervical cancer, CD3E was identified as a potential biomarker through database-based analysis [5].

In conclusion, Cd3e is essential for T cell receptor signaling and T cell-mediated immune responses. Gene-edited mouse models, such as CD3E humanized mice, have provided valuable insights into the role of Cd3e in cancer immunotherapy, T-cell subset regulation, and as a biomarker in specific cancers, facilitating a better understanding of related biological processes and disease mechanisms.