CD58 (lymphocyte function-associated antigen-3, LFA-3) is a cell surface glycoprotein that serves as a costimulatory receptor through its interaction with CD2 on T cells and NK cells 1. This CD2-CD58 interaction is crucial for forming the immunological synapse, promoting T/NK cell activation, proliferation, and enhancing cytotoxic responses 12. CD58 functions by localizing to the outer edge of the immunological synapse in a 'CD2 corolla' pattern, where it amplifies TCR signaling by 77% and integrates multiple costimulatory signals 3. Mechanistically, CD58 regulates immune responses through the LYN/CD22/SHP1 signaling axis, which inhibits JAK2/STAT1 pathway activity and limits PDL1 and IDO expression 4. Loss or downregulation of CD58 enables tumor immune evasion by reducing T/NK cell activation and increasing immunosuppressive molecule expression 54. In diffuse large B-cell lymphoma, CD58 alterations (9.1% mutations, 44.7% copy number losses) correlate with poor therapeutic responses and survival outcomes 4. CD58 genetic variants also provide protective effects against multiple sclerosis, particularly in Caucasian populations 6. The molecule exists in both membrane-bound and soluble forms, with soluble CD58 potentially contributing to immunosuppression in tumor microenvironments 1.