Unique amongst lymphomas, classical Hodgkin lymphoma is characterized by a relatively rare population of malignant Hodgkin Reed-Sternberg cells surrounded by a dense tumor immune microenvironment (TME), the role of which remains undefined. The composition of the TME includes T and B lymphocytes, macrophages, plasma cells, eosinophils, and stroma, with the nature of the infiltrate varying by histological subtype.
Dr. Ralf Küppers will review how overcoming challenges of targeted deep sequencing or whole exome sequencing created by the rarity of Reed-Sternberg cells within tumor specimens has led to insights into the landscape of somatic mutations involved in the pathogenesis of Hodgkin lymphoma. Initial results have highlighted the importance of genetic dysregulation of the NF-κB and JAK/STAT pathways and various means of immune evasion. These genetic factors may directly and indirectly influence the TME. He will also outline additional work using exome sequencing that has elucidated the molecular pathogenesis and patterns of shared and distinct mutations in composite Hodgkin and B-cell non-Hodgkin lymphomas.
Dr. Maher Gandhi will summarize current knowledge of the Hodgkin TME and immune checkpoints in classical Hodgkin lymphoma in light of the reignited debate about the role of adaptive and innate immunity in this disease. He will also outline mechanisms by which Reed-Sternberg cells are able to evade host anti-tumor immunity and describe how this knowledge may lead to new insights in understanding prognosis and improving therapy.
Dr. Barbara Savoldo will highlight key aspects of innovations in immunotherapy that are relevant to the treatment of Hodgkin lymphoma including novel agents, combinations, and strategies to overcome treatment resistance. Engineering of chimeric antigen receptors (CARs) in T cells has propelled the clinical application of tumor specific cells in B cell malignancies, and this approach is now moving to Hodgkin lymphoma by targeting CD30. Given the unique biology of Hodgkin lymphoma, Dr. Savoldo will summarize early clinical data and describe CAR modifications which may enhance migration and trafficking to the tumor for greater therapeutic effect.