Overcoming the Immunosuppressive Tumor Microenvironment of Hodgkin Lymphoma Using Chimeric Antigen Receptor T Cells [Research Articles]

Some patients with otherwise treatment-resistant Hodgkin lymphoma (HL) could benefit from chimeric antigen receptor T cell (CART) therapy. However, HL lacks CD19 and contains a highly immunosuppressive tumor microenvironment (TME). We hypothesized that in HL, CART should target both malignant cells and the TME. We demonstrated CD123 on both HL cells and TME, including tumor-associated macrophages (TAM). In vitro, HL cells convert macrophages towards immunosuppressive TAM that inhibit T cell proliferation. In contrast, anti-CD123 CART recognized and killed TAM thus overcoming immunosuppression. Finally, we showed in immunodeficient mouse models that CART123 eradicate HL, and establish long-term immune memory. A novel platform that targets malignant cells and the microenvironment may be needed to successfully treat malignancies with an immunosuppressive milieu.

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