The Tumor Microenvironment Regulates CD19 and CD20 Immunotherapy for Lymphoma

B cells have diverse functions during immune responses, including antibody production, antigen presentation, and cytokine secretion. Multiple lymphomas and leukemias derive from malignant B cells, so therapies that deplete B cells are clinically important, particularly antibodies targeting the B cell–specific surface molecules CD19 and CD20. Macrophages are the principal mediators of CD19 and CD20 monoclonal antibody–dependent B-cell and lymphoma depletion in mice through Fcγ receptor–dependent phagocytosis. Thereby, the extent of CD19 or CD20 antibody–induced B cell and tumor depletion in vivo is influenced by molecular changes within tumors and genetic variations between individuals. In addition to Fcγ receptor polymorphisms, lymphoma- and regulatory B cell–derived cytokine production and macrophage localization and function within tumor microenvironments influence tumor clearance. Given the dynamic interactions of these factors, the identification of effector cell and tumor microenvironment genetic alterations will identify molecular targets that enhance immunotherapies for the treatment of human diseases.