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Hodgkin’s Disease (HD) has a unique histology since only a few neoplastic cells are surrounded by inflammatory accessory cells that in the last years have emerged as crucial players in sustaining the course of disease. In addition, recent studies suggest that the abnormal activity of these inflammatory cells (such as deregulation in Tregsignaling, expansion of myeloid derived suppressor cells, HLA-G signaling and NK dysfunction) may have prognostic significance. This review is focused on summarizing recent advanced in immunological defects in HD with translational implications.