Prognostic Impact of CD57⁺ Natural Killer Cells and CD138⁺ Plasma Cells as Minor Components of the Tumor Microenvironment in Mixed Cellularity Classical Hodgkin Lymphoma

The tumor microenvironment (TME) plays a crucial role in tumor progression and treatment response of classical Hodgkin lymphoma (CHL). Although the contribution of major immune cells like T lymphocytes and macrophages has been widely studied, the prognostic impact of minor populations such as natural killer (NK) cells and plasma cells remains unclear. This study investigates the prognostic significance of plasma cells and NK cells in the TME of CHL, using CD138 and CD57 immunostaining, respectively. A retrospective analysis was conducted on 50 cases of CHL of the mixed cellularity subtype. Specimens were obtained as formalin-fixed, paraffin-embedded (FFPE) blocks from the Pathology Department of the South Egypt Cancer Institute, Assiut University. Immunohistochemical staining for CD57 and CD138 was performed to evaluate NK cells and plasma cells within the TME. A tumor immune profiling was proposed to assess its prognostic significance, based on digital quantification of immune cell infiltration. High CD57+ NK cell infiltration was significantly associated with favorable clinical features, including early-stage disease, absence of B symptoms, good treatment response, and improved overall survival. In contrast, high CD138+ plasma cell expression was associated with advanced-stage disease. These findings suggest that CD57+ NK cells and CD138+ plasma cells may contribute to the prognostic landscape of CHL. Understanding the functional roles of these cells within the TME may enable more personalized and immune-informed strategies for CHL patients.