Abstract
Multiple myeloma (MM) is a refractory hematologic malignancy driven by clonal plasma cell proliferation and a complex bone marrow microenvironment. CD81, a tetraspanin protein, has been implicated in immune regulation and cancer progression, but its role in MM remains unclear. This study investigated the prognostic significance of CD81 expression and its relationship with immune cells in 178 newly diagnosed MM patients. CD81 positivity (60.67%) was associated with reduced overall survival (OS) but not progression-free survival (PFS). High CD81 expression correlated with decreased peripheral CD8 + T cell counts and increased M2 macrophage infiltration (CD206+), both linked to poorer outcomes. Conversely, high CD68 expression (pan-macrophage marker) was associated with improved prognosis, potentially reflecting favorable M1 macrophage activity. These findings highlight CD81 as a prognostic marker in MM, influencing immune cell dynamics and clinical outcomes. The interplay between CD81, M2 macrophages, and CD8 + T cells underscores the complexity of the MM immune microenvironment, suggesting novel therapeutic targets. Further studies are needed to elucidate CD81's mechanistic role in immune modulation.